PubMed:11106653 JSONTXT

{"project":"CL-cell","denotations":[{"id":"T1","span":{"begin":905,"end":910},"obj":"Cell"},{"id":"T2","span":{"begin":940,"end":945},"obj":"Cell"},{"id":"T3","span":{"begin":1116,"end":1121},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0004124"},{"id":"A2","pred":"cl_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL:0004124"},{"id":"A3","pred":"cl_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CL:0004124"}],"text":"Amyloid-beta interactions with chondroitin sulfate-derived monosaccharides and disaccharides. implications for drug development.\nIn Alzheimer's disease, the major pathological features are diffuse and senile plaques that are primarily composed of the amyloid-beta (A beta) peptide. It has been proposed that proteoglycans and glycosaminoglycans (GAG) facilitate amyloid fibril formation and/or stabilize the plaque aggregates. To develop effective therapeutics based on A beta-GAG interactions, understanding the A beta binding motif on the GAG chain is imperative. Using electron microscopy, fluorescence spectroscopy, and competitive inhibition ELISAs, we have evaluated the ability of chondroitin sulfate-derived monosaccharides and disaccharides to induce the structural changes in A beta that are associated with GAG interactions. Our results demonstrate that the disaccharides GalNAc-4-sulfate(4S), Delta UA-GalNAc-6-sulfate(6S), and Delta UA-GalNAc-4,6-sulfate(4S,6S), the iduronic acid-2-sulfate analogues, and the monosaccharides d-GalNAc-4S, d-GalNAc-6S, and d-GalNAc-4S,6S, but not d-GalNAc, d-GlcNAc, or Delta UA-GalNAc, induce the fibrillar features of A beta-GAG interactions. The binding affinities of all chondroitin sulfate-derived saccharides mimic those of the intact GAG chains. The sulfated monosaccharides and disaccharides compete with the intact chondroitin sulfate and heparin GAGs for A beta binding, as illustrated by competitive inhibition ELISAs. Therefore, the development of therapeutics based on the model of A beta-chondroitin sulfate binding may lead to effective inhibitors of the GAG-induced amyloid formation that is observed in vitro."}

{"project":"GlyCosmos6-Glycan-Motif-Image","denotations":[{"id":"T1","span":{"begin":31,"end":42},"obj":"Glycan_Motif"},{"id":"T2","span":{"begin":688,"end":699},"obj":"Glycan_Motif"},{"id":"T3","span":{"begin":1221,"end":1232},"obj":"Glycan_Motif"},{"id":"T4","span":{"begin":1370,"end":1381},"obj":"Glycan_Motif"},{"id":"T5","span":{"begin":1394,"end":1401},"obj":"Glycan_Motif"},{"id":"T7","span":{"begin":1548,"end":1559},"obj":"Glycan_Motif"}],"attributes":[{"id":"A1","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G43702JT"},{"id":"A2","pred":"image","subj":"T2","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G43702JT"},{"id":"A3","pred":"image","subj":"T3","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G43702JT"},{"id":"A4","pred":"image","subj":"T4","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G43702JT"},{"id":"A5","pred":"image","subj":"T5","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G54161DR"},{"id":"A6","pred":"image","subj":"T5","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G00021MO"},{"id":"A7","pred":"image","subj":"T7","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G43702JT"}],"text":"Amyloid-beta interactions with chondroitin sulfate-derived monosaccharides and disaccharides. implications for drug development.\nIn Alzheimer's disease, the major pathological features are diffuse and senile plaques that are primarily composed of the amyloid-beta (A beta) peptide. It has been proposed that proteoglycans and glycosaminoglycans (GAG) facilitate amyloid fibril formation and/or stabilize the plaque aggregates. To develop effective therapeutics based on A beta-GAG interactions, understanding the A beta binding motif on the GAG chain is imperative. Using electron microscopy, fluorescence spectroscopy, and competitive inhibition ELISAs, we have evaluated the ability of chondroitin sulfate-derived monosaccharides and disaccharides to induce the structural changes in A beta that are associated with GAG interactions. Our results demonstrate that the disaccharides GalNAc-4-sulfate(4S), Delta UA-GalNAc-6-sulfate(6S), and Delta UA-GalNAc-4,6-sulfate(4S,6S), the iduronic acid-2-sulfate analogues, and the monosaccharides d-GalNAc-4S, d-GalNAc-6S, and d-GalNAc-4S,6S, but not d-GalNAc, d-GlcNAc, or Delta UA-GalNAc, induce the fibrillar features of A beta-GAG interactions. The binding affinities of all chondroitin sulfate-derived saccharides mimic those of the intact GAG chains. The sulfated monosaccharides and disaccharides compete with the intact chondroitin sulfate and heparin GAGs for A beta binding, as illustrated by competitive inhibition ELISAs. Therefore, the development of therapeutics based on the model of A beta-chondroitin sulfate binding may lead to effective inhibitors of the GAG-induced amyloid formation that is observed in vitro."}

{"project":"Glycosmos6-GlycoEpitope","denotations":[{"id":"T1","span":{"begin":31,"end":42},"obj":"http://www.glycoepitope.jp/epitopes/EP0081"},{"id":"T2","span":{"begin":688,"end":699},"obj":"http://www.glycoepitope.jp/epitopes/EP0081"},{"id":"T3","span":{"begin":1221,"end":1232},"obj":"http://www.glycoepitope.jp/epitopes/EP0081"},{"id":"T4","span":{"begin":1370,"end":1381},"obj":"http://www.glycoepitope.jp/epitopes/EP0081"},{"id":"T5","span":{"begin":1548,"end":1559},"obj":"http://www.glycoepitope.jp/epitopes/EP0081"}],"text":"Amyloid-beta interactions with chondroitin sulfate-derived monosaccharides and disaccharides. implications for drug development.\nIn Alzheimer's disease, the major pathological features are diffuse and senile plaques that are primarily composed of the amyloid-beta (A beta) peptide. It has been proposed that proteoglycans and glycosaminoglycans (GAG) facilitate amyloid fibril formation and/or stabilize the plaque aggregates. To develop effective therapeutics based on A beta-GAG interactions, understanding the A beta binding motif on the GAG chain is imperative. Using electron microscopy, fluorescence spectroscopy, and competitive inhibition ELISAs, we have evaluated the ability of chondroitin sulfate-derived monosaccharides and disaccharides to induce the structural changes in A beta that are associated with GAG interactions. Our results demonstrate that the disaccharides GalNAc-4-sulfate(4S), Delta UA-GalNAc-6-sulfate(6S), and Delta UA-GalNAc-4,6-sulfate(4S,6S), the iduronic acid-2-sulfate analogues, and the monosaccharides d-GalNAc-4S, d-GalNAc-6S, and d-GalNAc-4S,6S, but not d-GalNAc, d-GlcNAc, or Delta UA-GalNAc, induce the fibrillar features of A beta-GAG interactions. The binding affinities of all chondroitin sulfate-derived saccharides mimic those of the intact GAG chains. The sulfated monosaccharides and disaccharides compete with the intact chondroitin sulfate and heparin GAGs for A beta binding, as illustrated by competitive inhibition ELISAs. Therefore, the development of therapeutics based on the model of A beta-chondroitin sulfate binding may lead to effective inhibitors of the GAG-induced amyloid formation that is observed in vitro."}

{"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":128},"obj":"Sentence"},{"id":"T2","span":{"begin":129,"end":281},"obj":"Sentence"},{"id":"T3","span":{"begin":282,"end":426},"obj":"Sentence"},{"id":"T4","span":{"begin":427,"end":565},"obj":"Sentence"},{"id":"T5","span":{"begin":566,"end":835},"obj":"Sentence"},{"id":"T6","span":{"begin":836,"end":1190},"obj":"Sentence"},{"id":"T7","span":{"begin":1191,"end":1298},"obj":"Sentence"},{"id":"T8","span":{"begin":1299,"end":1475},"obj":"Sentence"},{"id":"T9","span":{"begin":1476,"end":1672},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Amyloid-beta interactions with chondroitin sulfate-derived monosaccharides and disaccharides. implications for drug development.\nIn Alzheimer's disease, the major pathological features are diffuse and senile plaques that are primarily composed of the amyloid-beta (A beta) peptide. It has been proposed that proteoglycans and glycosaminoglycans (GAG) facilitate amyloid fibril formation and/or stabilize the plaque aggregates. To develop effective therapeutics based on A beta-GAG interactions, understanding the A beta binding motif on the GAG chain is imperative. Using electron microscopy, fluorescence spectroscopy, and competitive inhibition ELISAs, we have evaluated the ability of chondroitin sulfate-derived monosaccharides and disaccharides to induce the structural changes in A beta that are associated with GAG interactions. Our results demonstrate that the disaccharides GalNAc-4-sulfate(4S), Delta UA-GalNAc-6-sulfate(6S), and Delta UA-GalNAc-4,6-sulfate(4S,6S), the iduronic acid-2-sulfate analogues, and the monosaccharides d-GalNAc-4S, d-GalNAc-6S, and d-GalNAc-4S,6S, but not d-GalNAc, d-GlcNAc, or Delta UA-GalNAc, induce the fibrillar features of A beta-GAG interactions. The binding affinities of all chondroitin sulfate-derived saccharides mimic those of the intact GAG chains. The sulfated monosaccharides and disaccharides compete with the intact chondroitin sulfate and heparin GAGs for A beta binding, as illustrated by competitive inhibition ELISAs. Therefore, the development of therapeutics based on the model of A beta-chondroitin sulfate binding may lead to effective inhibitors of the GAG-induced amyloid formation that is observed in vitro."}

{"project":"GlyCosmos6-Glycan-Motif-Structure","denotations":[{"id":"T1","span":{"begin":31,"end":42},"obj":"https://glytoucan.org/Structures/Glycans/G43702JT"},{"id":"T2","span":{"begin":688,"end":699},"obj":"https://glytoucan.org/Structures/Glycans/G43702JT"},{"id":"T3","span":{"begin":1221,"end":1232},"obj":"https://glytoucan.org/Structures/Glycans/G43702JT"},{"id":"T4","span":{"begin":1370,"end":1381},"obj":"https://glytoucan.org/Structures/Glycans/G43702JT"},{"id":"T5","span":{"begin":1394,"end":1401},"obj":"https://glytoucan.org/Structures/Glycans/G00021MO"},{"id":"T6","span":{"begin":1394,"end":1401},"obj":"https://glytoucan.org/Structures/Glycans/G54161DR"},{"id":"T7","span":{"begin":1548,"end":1559},"obj":"https://glytoucan.org/Structures/Glycans/G43702JT"}],"text":"Amyloid-beta interactions with chondroitin sulfate-derived monosaccharides and disaccharides. implications for drug development.\nIn Alzheimer's disease, the major pathological features are diffuse and senile plaques that are primarily composed of the amyloid-beta (A beta) peptide. It has been proposed that proteoglycans and glycosaminoglycans (GAG) facilitate amyloid fibril formation and/or stabilize the plaque aggregates. To develop effective therapeutics based on A beta-GAG interactions, understanding the A beta binding motif on the GAG chain is imperative. Using electron microscopy, fluorescence spectroscopy, and competitive inhibition ELISAs, we have evaluated the ability of chondroitin sulfate-derived monosaccharides and disaccharides to induce the structural changes in A beta that are associated with GAG interactions. Our results demonstrate that the disaccharides GalNAc-4-sulfate(4S), Delta UA-GalNAc-6-sulfate(6S), and Delta UA-GalNAc-4,6-sulfate(4S,6S), the iduronic acid-2-sulfate analogues, and the monosaccharides d-GalNAc-4S, d-GalNAc-6S, and d-GalNAc-4S,6S, but not d-GalNAc, d-GlcNAc, or Delta UA-GalNAc, induce the fibrillar features of A beta-GAG interactions. The binding affinities of all chondroitin sulfate-derived saccharides mimic those of the intact GAG chains. The sulfated monosaccharides and disaccharides compete with the intact chondroitin sulfate and heparin GAGs for A beta binding, as illustrated by competitive inhibition ELISAs. Therefore, the development of therapeutics based on the model of A beta-chondroitin sulfate binding may lead to effective inhibitors of the GAG-induced amyloid formation that is observed in vitro."}

{"project":"NGLY1-deficiency","denotations":[{"id":"PD-NGLY1-deficiency-B_T1","span":{"begin":1105,"end":1111},"obj":"chem:24139"}],"namespaces":[{"prefix":"hgnc","uri":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:"},{"prefix":"omim","uri":"https://www.omim.org/entry/"},{"prefix":"chem","uri":"https://pubchem.ncbi.nlm.nih.gov/compound/"}],"text":"Amyloid-beta interactions with chondroitin sulfate-derived monosaccharides and disaccharides. implications for drug development.\nIn Alzheimer's disease, the major pathological features are diffuse and senile plaques that are primarily composed of the amyloid-beta (A beta) peptide. It has been proposed that proteoglycans and glycosaminoglycans (GAG) facilitate amyloid fibril formation and/or stabilize the plaque aggregates. To develop effective therapeutics based on A beta-GAG interactions, understanding the A beta binding motif on the GAG chain is imperative. Using electron microscopy, fluorescence spectroscopy, and competitive inhibition ELISAs, we have evaluated the ability of chondroitin sulfate-derived monosaccharides and disaccharides to induce the structural changes in A beta that are associated with GAG interactions. Our results demonstrate that the disaccharides GalNAc-4-sulfate(4S), Delta UA-GalNAc-6-sulfate(6S), and Delta UA-GalNAc-4,6-sulfate(4S,6S), the iduronic acid-2-sulfate analogues, and the monosaccharides d-GalNAc-4S, d-GalNAc-6S, and d-GalNAc-4S,6S, but not d-GalNAc, d-GlcNAc, or Delta UA-GalNAc, induce the fibrillar features of A beta-GAG interactions. The binding affinities of all chondroitin sulfate-derived saccharides mimic those of the intact GAG chains. The sulfated monosaccharides and disaccharides compete with the intact chondroitin sulfate and heparin GAGs for A beta binding, as illustrated by competitive inhibition ELISAs. Therefore, the development of therapeutics based on the model of A beta-chondroitin sulfate binding may lead to effective inhibitors of the GAG-induced amyloid formation that is observed in vitro."}

{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":0,"end":7},"obj":"Disease"},{"id":"T2","span":{"begin":132,"end":151},"obj":"Disease"},{"id":"T3","span":{"begin":251,"end":258},"obj":"Disease"},{"id":"T4","span":{"begin":362,"end":369},"obj":"Disease"},{"id":"T5","span":{"begin":1628,"end":1635},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0019065"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0004975"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0019065"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MONDO_0019065"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/MONDO_0019065"}],"text":"Amyloid-beta interactions with chondroitin sulfate-derived monosaccharides and disaccharides. implications for drug development.\nIn Alzheimer's disease, the major pathological features are diffuse and senile plaques that are primarily composed of the amyloid-beta (A beta) peptide. It has been proposed that proteoglycans and glycosaminoglycans (GAG) facilitate amyloid fibril formation and/or stabilize the plaque aggregates. To develop effective therapeutics based on A beta-GAG interactions, understanding the A beta binding motif on the GAG chain is imperative. Using electron microscopy, fluorescence spectroscopy, and competitive inhibition ELISAs, we have evaluated the ability of chondroitin sulfate-derived monosaccharides and disaccharides to induce the structural changes in A beta that are associated with GAG interactions. Our results demonstrate that the disaccharides GalNAc-4-sulfate(4S), Delta UA-GalNAc-6-sulfate(6S), and Delta UA-GalNAc-4,6-sulfate(4S,6S), the iduronic acid-2-sulfate analogues, and the monosaccharides d-GalNAc-4S, d-GalNAc-6S, and d-GalNAc-4S,6S, but not d-GalNAc, d-GlcNAc, or Delta UA-GalNAc, induce the fibrillar features of A beta-GAG interactions. The binding affinities of all chondroitin sulfate-derived saccharides mimic those of the intact GAG chains. The sulfated monosaccharides and disaccharides compete with the intact chondroitin sulfate and heparin GAGs for A beta binding, as illustrated by competitive inhibition ELISAs. Therefore, the development of therapeutics based on the model of A beta-chondroitin sulfate binding may lead to effective inhibitors of the GAG-induced amyloid formation that is observed in vitro."}

{"project":"HP-phenotype","denotations":[{"id":"T1","span":{"begin":132,"end":151},"obj":"Phenotype"},{"id":"T2","span":{"begin":201,"end":215},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0002511"},{"id":"A2","pred":"hp_id","subj":"T2","obj":"HP:0100256"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}],"text":"Amyloid-beta interactions with chondroitin sulfate-derived monosaccharides and disaccharides. implications for drug development.\nIn Alzheimer's disease, the major pathological features are diffuse and senile plaques that are primarily composed of the amyloid-beta (A beta) peptide. It has been proposed that proteoglycans and glycosaminoglycans (GAG) facilitate amyloid fibril formation and/or stabilize the plaque aggregates. To develop effective therapeutics based on A beta-GAG interactions, understanding the A beta binding motif on the GAG chain is imperative. Using electron microscopy, fluorescence spectroscopy, and competitive inhibition ELISAs, we have evaluated the ability of chondroitin sulfate-derived monosaccharides and disaccharides to induce the structural changes in A beta that are associated with GAG interactions. Our results demonstrate that the disaccharides GalNAc-4-sulfate(4S), Delta UA-GalNAc-6-sulfate(6S), and Delta UA-GalNAc-4,6-sulfate(4S,6S), the iduronic acid-2-sulfate analogues, and the monosaccharides d-GalNAc-4S, d-GalNAc-6S, and d-GalNAc-4S,6S, but not d-GalNAc, d-GlcNAc, or Delta UA-GalNAc, induce the fibrillar features of A beta-GAG interactions. The binding affinities of all chondroitin sulfate-derived saccharides mimic those of the intact GAG chains. The sulfated monosaccharides and disaccharides compete with the intact chondroitin sulfate and heparin GAGs for A beta binding, as illustrated by competitive inhibition ELISAs. Therefore, the development of therapeutics based on the model of A beta-chondroitin sulfate binding may lead to effective inhibitors of the GAG-induced amyloid formation that is observed in vitro."}

{"project":"Glycan-GlyCosmos","denotations":[{"id":"T1","span":{"begin":31,"end":42},"obj":"Glycan"},{"id":"T2","span":{"begin":688,"end":699},"obj":"Glycan"},{"id":"T3","span":{"begin":883,"end":889},"obj":"Glycan"},{"id":"T4","span":{"begin":914,"end":920},"obj":"Glycan"},{"id":"T5","span":{"begin":949,"end":955},"obj":"Glycan"},{"id":"T6","span":{"begin":1041,"end":1047},"obj":"Glycan"},{"id":"T7","span":{"begin":1054,"end":1060},"obj":"Glycan"},{"id":"T8","span":{"begin":1071,"end":1077},"obj":"Glycan"},{"id":"T9","span":{"begin":1095,"end":1101},"obj":"Glycan"},{"id":"T10","span":{"begin":1125,"end":1131},"obj":"Glycan"},{"id":"T11","span":{"begin":1221,"end":1232},"obj":"Glycan"},{"id":"T12","span":{"begin":1370,"end":1381},"obj":"Glycan"},{"id":"T13","span":{"begin":1548,"end":1559},"obj":"Glycan"}],"attributes":[{"id":"A1","pred":"glycosmos_id","subj":"T1","obj":"https://glycosmos.org/glycans/show/G43702JT"},{"id":"A14","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G43702JT"},{"id":"A2","pred":"glycosmos_id","subj":"T2","obj":"https://glycosmos.org/glycans/show/G43702JT"},{"id":"A15","pred":"image","subj":"T2","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G43702JT"},{"id":"A3","pred":"glycosmos_id","subj":"T3","obj":"https://glycosmos.org/glycans/show/G39738WL"},{"id":"A16","pred":"image","subj":"T3","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G39738WL"},{"id":"A4","pred":"glycosmos_id","subj":"T4","obj":"https://glycosmos.org/glycans/show/G39738WL"},{"id":"A17","pred":"image","subj":"T4","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G39738WL"},{"id":"A5","pred":"glycosmos_id","subj":"T5","obj":"https://glycosmos.org/glycans/show/G39738WL"},{"id":"A18","pred":"image","subj":"T5","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G39738WL"},{"id":"A6","pred":"glycosmos_id","subj":"T6","obj":"https://glycosmos.org/glycans/show/G39738WL"},{"id":"A19","pred":"image","subj":"T6","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G39738WL"},{"id":"A7","pred":"glycosmos_id","subj":"T7","obj":"https://glycosmos.org/glycans/show/G39738WL"},{"id":"A20","pred":"image","subj":"T7","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G39738WL"},{"id":"A8","pred":"glycosmos_id","subj":"T8","obj":"https://glycosmos.org/glycans/show/G39738WL"},{"id":"A21","pred":"image","subj":"T8","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G39738WL"},{"id":"A9","pred":"glycosmos_id","subj":"T9","obj":"https://glycosmos.org/glycans/show/G39738WL"},{"id":"A22","pred":"image","subj":"T9","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G39738WL"},{"id":"A10","pred":"glycosmos_id","subj":"T10","obj":"https://glycosmos.org/glycans/show/G39738WL"},{"id":"A23","pred":"image","subj":"T10","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G39738WL"},{"id":"A11","pred":"glycosmos_id","subj":"T11","obj":"https://glycosmos.org/glycans/show/G43702JT"},{"id":"A24","pred":"image","subj":"T11","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G43702JT"},{"id":"A12","pred":"glycosmos_id","subj":"T12","obj":"https://glycosmos.org/glycans/show/G43702JT"},{"id":"A25","pred":"image","subj":"T12","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G43702JT"},{"id":"A13","pred":"glycosmos_id","subj":"T13","obj":"https://glycosmos.org/glycans/show/G43702JT"},{"id":"A26","pred":"image","subj":"T13","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G43702JT"}],"text":"Amyloid-beta interactions with chondroitin sulfate-derived monosaccharides and disaccharides. implications for drug development.\nIn Alzheimer's disease, the major pathological features are diffuse and senile plaques that are primarily composed of the amyloid-beta (A beta) peptide. It has been proposed that proteoglycans and glycosaminoglycans (GAG) facilitate amyloid fibril formation and/or stabilize the plaque aggregates. To develop effective therapeutics based on A beta-GAG interactions, understanding the A beta binding motif on the GAG chain is imperative. Using electron microscopy, fluorescence spectroscopy, and competitive inhibition ELISAs, we have evaluated the ability of chondroitin sulfate-derived monosaccharides and disaccharides to induce the structural changes in A beta that are associated with GAG interactions. Our results demonstrate that the disaccharides GalNAc-4-sulfate(4S), Delta UA-GalNAc-6-sulfate(6S), and Delta UA-GalNAc-4,6-sulfate(4S,6S), the iduronic acid-2-sulfate analogues, and the monosaccharides d-GalNAc-4S, d-GalNAc-6S, and d-GalNAc-4S,6S, but not d-GalNAc, d-GlcNAc, or Delta UA-GalNAc, induce the fibrillar features of A beta-GAG interactions. The binding affinities of all chondroitin sulfate-derived saccharides mimic those of the intact GAG chains. The sulfated monosaccharides and disaccharides compete with the intact chondroitin sulfate and heparin GAGs for A beta binding, as illustrated by competitive inhibition ELISAs. Therefore, the development of therapeutics based on the model of A beta-chondroitin sulfate binding may lead to effective inhibitors of the GAG-induced amyloid formation that is observed in vitro."}

{"project":"GlyCosmos-GlycoEpitope","denotations":[{"id":"T1","span":{"begin":31,"end":42},"obj":"http://purl.jp/bio/12/glyco/glycan#Glycan_epitope"},{"id":"T2","span":{"begin":688,"end":699},"obj":"http://purl.jp/bio/12/glyco/glycan#Glycan_epitope"},{"id":"T3","span":{"begin":1221,"end":1232},"obj":"http://purl.jp/bio/12/glyco/glycan#Glycan_epitope"},{"id":"T4","span":{"begin":1370,"end":1381},"obj":"http://purl.jp/bio/12/glyco/glycan#Glycan_epitope"},{"id":"T5","span":{"begin":1548,"end":1559},"obj":"http://purl.jp/bio/12/glyco/glycan#Glycan_epitope"}],"attributes":[{"id":"A1","pred":"glycoepitope_id","subj":"T1","obj":"http://www.glycoepitope.jp/epitopes/EP0081"},{"id":"A2","pred":"glycoepitope_id","subj":"T2","obj":"http://www.glycoepitope.jp/epitopes/EP0081"},{"id":"A3","pred":"glycoepitope_id","subj":"T3","obj":"http://www.glycoepitope.jp/epitopes/EP0081"},{"id":"A4","pred":"glycoepitope_id","subj":"T4","obj":"http://www.glycoepitope.jp/epitopes/EP0081"},{"id":"A5","pred":"glycoepitope_id","subj":"T5","obj":"http://www.glycoepitope.jp/epitopes/EP0081"}],"text":"Amyloid-beta interactions with chondroitin sulfate-derived monosaccharides and disaccharides. implications for drug development.\nIn Alzheimer's disease, the major pathological features are diffuse and senile plaques that are primarily composed of the amyloid-beta (A beta) peptide. It has been proposed that proteoglycans and glycosaminoglycans (GAG) facilitate amyloid fibril formation and/or stabilize the plaque aggregates. To develop effective therapeutics based on A beta-GAG interactions, understanding the A beta binding motif on the GAG chain is imperative. Using electron microscopy, fluorescence spectroscopy, and competitive inhibition ELISAs, we have evaluated the ability of chondroitin sulfate-derived monosaccharides and disaccharides to induce the structural changes in A beta that are associated with GAG interactions. Our results demonstrate that the disaccharides GalNAc-4-sulfate(4S), Delta UA-GalNAc-6-sulfate(6S), and Delta UA-GalNAc-4,6-sulfate(4S,6S), the iduronic acid-2-sulfate analogues, and the monosaccharides d-GalNAc-4S, d-GalNAc-6S, and d-GalNAc-4S,6S, but not d-GalNAc, d-GlcNAc, or Delta UA-GalNAc, induce the fibrillar features of A beta-GAG interactions. The binding affinities of all chondroitin sulfate-derived saccharides mimic those of the intact GAG chains. The sulfated monosaccharides and disaccharides compete with the intact chondroitin sulfate and heparin GAGs for A beta binding, as illustrated by competitive inhibition ELISAs. Therefore, the development of therapeutics based on the model of A beta-chondroitin sulfate binding may lead to effective inhibitors of the GAG-induced amyloid formation that is observed in vitro."}

{"project":"GlyCosmos15-HP","denotations":[{"id":"T1","span":{"begin":132,"end":151},"obj":"Phenotype"},{"id":"T2","span":{"begin":201,"end":215},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0002511"},{"id":"A2","pred":"hp_id","subj":"T2","obj":"HP:0100256"}],"text":"Amyloid-beta interactions with chondroitin sulfate-derived monosaccharides and disaccharides. implications for drug development.\nIn Alzheimer's disease, the major pathological features are diffuse and senile plaques that are primarily composed of the amyloid-beta (A beta) peptide. It has been proposed that proteoglycans and glycosaminoglycans (GAG) facilitate amyloid fibril formation and/or stabilize the plaque aggregates. To develop effective therapeutics based on A beta-GAG interactions, understanding the A beta binding motif on the GAG chain is imperative. Using electron microscopy, fluorescence spectroscopy, and competitive inhibition ELISAs, we have evaluated the ability of chondroitin sulfate-derived monosaccharides and disaccharides to induce the structural changes in A beta that are associated with GAG interactions. Our results demonstrate that the disaccharides GalNAc-4-sulfate(4S), Delta UA-GalNAc-6-sulfate(6S), and Delta UA-GalNAc-4,6-sulfate(4S,6S), the iduronic acid-2-sulfate analogues, and the monosaccharides d-GalNAc-4S, d-GalNAc-6S, and d-GalNAc-4S,6S, but not d-GalNAc, d-GlcNAc, or Delta UA-GalNAc, induce the fibrillar features of A beta-GAG interactions. The binding affinities of all chondroitin sulfate-derived saccharides mimic those of the intact GAG chains. The sulfated monosaccharides and disaccharides compete with the intact chondroitin sulfate and heparin GAGs for A beta binding, as illustrated by competitive inhibition ELISAs. Therefore, the development of therapeutics based on the model of A beta-chondroitin sulfate binding may lead to effective inhibitors of the GAG-induced amyloid formation that is observed in vitro."}

{"project":"GlyCosmos15-MONDO","denotations":[{"id":"T1","span":{"begin":0,"end":7},"obj":"Disease"},{"id":"T2","span":{"begin":132,"end":151},"obj":"Disease"},{"id":"T3","span":{"begin":251,"end":258},"obj":"Disease"},{"id":"T4","span":{"begin":362,"end":369},"obj":"Disease"},{"id":"T5","span":{"begin":1628,"end":1635},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0019065"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0004975"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0019065"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MONDO_0019065"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/MONDO_0019065"}],"text":"Amyloid-beta interactions with chondroitin sulfate-derived monosaccharides and disaccharides. implications for drug development.\nIn Alzheimer's disease, the major pathological features are diffuse and senile plaques that are primarily composed of the amyloid-beta (A beta) peptide. It has been proposed that proteoglycans and glycosaminoglycans (GAG) facilitate amyloid fibril formation and/or stabilize the plaque aggregates. To develop effective therapeutics based on A beta-GAG interactions, understanding the A beta binding motif on the GAG chain is imperative. Using electron microscopy, fluorescence spectroscopy, and competitive inhibition ELISAs, we have evaluated the ability of chondroitin sulfate-derived monosaccharides and disaccharides to induce the structural changes in A beta that are associated with GAG interactions. Our results demonstrate that the disaccharides GalNAc-4-sulfate(4S), Delta UA-GalNAc-6-sulfate(6S), and Delta UA-GalNAc-4,6-sulfate(4S,6S), the iduronic acid-2-sulfate analogues, and the monosaccharides d-GalNAc-4S, d-GalNAc-6S, and d-GalNAc-4S,6S, but not d-GalNAc, d-GlcNAc, or Delta UA-GalNAc, induce the fibrillar features of A beta-GAG interactions. The binding affinities of all chondroitin sulfate-derived saccharides mimic those of the intact GAG chains. The sulfated monosaccharides and disaccharides compete with the intact chondroitin sulfate and heparin GAGs for A beta binding, as illustrated by competitive inhibition ELISAs. Therefore, the development of therapeutics based on the model of A beta-chondroitin sulfate binding may lead to effective inhibitors of the GAG-induced amyloid formation that is observed in vitro."}

{"project":"GlyCosmos15-CL","denotations":[{"id":"T1","span":{"begin":905,"end":910},"obj":"Cell"},{"id":"T2","span":{"begin":940,"end":945},"obj":"Cell"},{"id":"T3","span":{"begin":1116,"end":1121},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0004124"},{"id":"A2","pred":"cl_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL:0004124"},{"id":"A3","pred":"cl_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CL:0004124"}],"text":"Amyloid-beta interactions with chondroitin sulfate-derived monosaccharides and disaccharides. implications for drug development.\nIn Alzheimer's disease, the major pathological features are diffuse and senile plaques that are primarily composed of the amyloid-beta (A beta) peptide. It has been proposed that proteoglycans and glycosaminoglycans (GAG) facilitate amyloid fibril formation and/or stabilize the plaque aggregates. To develop effective therapeutics based on A beta-GAG interactions, understanding the A beta binding motif on the GAG chain is imperative. Using electron microscopy, fluorescence spectroscopy, and competitive inhibition ELISAs, we have evaluated the ability of chondroitin sulfate-derived monosaccharides and disaccharides to induce the structural changes in A beta that are associated with GAG interactions. Our results demonstrate that the disaccharides GalNAc-4-sulfate(4S), Delta UA-GalNAc-6-sulfate(6S), and Delta UA-GalNAc-4,6-sulfate(4S,6S), the iduronic acid-2-sulfate analogues, and the monosaccharides d-GalNAc-4S, d-GalNAc-6S, and d-GalNAc-4S,6S, but not d-GalNAc, d-GlcNAc, or Delta UA-GalNAc, induce the fibrillar features of A beta-GAG interactions. The binding affinities of all chondroitin sulfate-derived saccharides mimic those of the intact GAG chains. The sulfated monosaccharides and disaccharides compete with the intact chondroitin sulfate and heparin GAGs for A beta binding, as illustrated by competitive inhibition ELISAs. Therefore, the development of therapeutics based on the model of A beta-chondroitin sulfate binding may lead to effective inhibitors of the GAG-induced amyloid formation that is observed in vitro."}

{"project":"GlyCosmos15-UBERON","denotations":[{"id":"T1","span":{"begin":370,"end":376},"obj":"Body_part"},{"id":"T2","span":{"begin":408,"end":414},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/GO_0099512"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0016482"}],"text":"Amyloid-beta interactions with chondroitin sulfate-derived monosaccharides and disaccharides. implications for drug development.\nIn Alzheimer's disease, the major pathological features are diffuse and senile plaques that are primarily composed of the amyloid-beta (A beta) peptide. It has been proposed that proteoglycans and glycosaminoglycans (GAG) facilitate amyloid fibril formation and/or stabilize the plaque aggregates. To develop effective therapeutics based on A beta-GAG interactions, understanding the A beta binding motif on the GAG chain is imperative. Using electron microscopy, fluorescence spectroscopy, and competitive inhibition ELISAs, we have evaluated the ability of chondroitin sulfate-derived monosaccharides and disaccharides to induce the structural changes in A beta that are associated with GAG interactions. Our results demonstrate that the disaccharides GalNAc-4-sulfate(4S), Delta UA-GalNAc-6-sulfate(6S), and Delta UA-GalNAc-4,6-sulfate(4S,6S), the iduronic acid-2-sulfate analogues, and the monosaccharides d-GalNAc-4S, d-GalNAc-6S, and d-GalNAc-4S,6S, but not d-GalNAc, d-GlcNAc, or Delta UA-GalNAc, induce the fibrillar features of A beta-GAG interactions. The binding affinities of all chondroitin sulfate-derived saccharides mimic those of the intact GAG chains. The sulfated monosaccharides and disaccharides compete with the intact chondroitin sulfate and heparin GAGs for A beta binding, as illustrated by competitive inhibition ELISAs. Therefore, the development of therapeutics based on the model of A beta-chondroitin sulfate binding may lead to effective inhibitors of the GAG-induced amyloid formation that is observed in vitro."}

{"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":128},"obj":"Sentence"},{"id":"T2","span":{"begin":129,"end":281},"obj":"Sentence"},{"id":"T3","span":{"begin":282,"end":426},"obj":"Sentence"},{"id":"T4","span":{"begin":427,"end":565},"obj":"Sentence"},{"id":"T5","span":{"begin":566,"end":835},"obj":"Sentence"},{"id":"T6","span":{"begin":836,"end":1190},"obj":"Sentence"},{"id":"T7","span":{"begin":1191,"end":1298},"obj":"Sentence"},{"id":"T8","span":{"begin":1299,"end":1475},"obj":"Sentence"},{"id":"T9","span":{"begin":1476,"end":1672},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Amyloid-beta interactions with chondroitin sulfate-derived monosaccharides and disaccharides. implications for drug development.\nIn Alzheimer's disease, the major pathological features are diffuse and senile plaques that are primarily composed of the amyloid-beta (A beta) peptide. It has been proposed that proteoglycans and glycosaminoglycans (GAG) facilitate amyloid fibril formation and/or stabilize the plaque aggregates. To develop effective therapeutics based on A beta-GAG interactions, understanding the A beta binding motif on the GAG chain is imperative. Using electron microscopy, fluorescence spectroscopy, and competitive inhibition ELISAs, we have evaluated the ability of chondroitin sulfate-derived monosaccharides and disaccharides to induce the structural changes in A beta that are associated with GAG interactions. Our results demonstrate that the disaccharides GalNAc-4-sulfate(4S), Delta UA-GalNAc-6-sulfate(6S), and Delta UA-GalNAc-4,6-sulfate(4S,6S), the iduronic acid-2-sulfate analogues, and the monosaccharides d-GalNAc-4S, d-GalNAc-6S, and d-GalNAc-4S,6S, but not d-GalNAc, d-GlcNAc, or Delta UA-GalNAc, induce the fibrillar features of A beta-GAG interactions. The binding affinities of all chondroitin sulfate-derived saccharides mimic those of the intact GAG chains. The sulfated monosaccharides and disaccharides compete with the intact chondroitin sulfate and heparin GAGs for A beta binding, as illustrated by competitive inhibition ELISAs. Therefore, the development of therapeutics based on the model of A beta-chondroitin sulfate binding may lead to effective inhibitors of the GAG-induced amyloid formation that is observed in vitro."}

{"project":"GlyCosmos15-Sentences","blocks":[{"id":"T1","span":{"begin":0,"end":128},"obj":"Sentence"},{"id":"T2","span":{"begin":129,"end":281},"obj":"Sentence"},{"id":"T3","span":{"begin":282,"end":426},"obj":"Sentence"},{"id":"T4","span":{"begin":427,"end":565},"obj":"Sentence"},{"id":"T5","span":{"begin":566,"end":835},"obj":"Sentence"},{"id":"T6","span":{"begin":836,"end":1190},"obj":"Sentence"},{"id":"T7","span":{"begin":1191,"end":1298},"obj":"Sentence"},{"id":"T8","span":{"begin":1299,"end":1475},"obj":"Sentence"},{"id":"T9","span":{"begin":1476,"end":1672},"obj":"Sentence"}],"text":"Amyloid-beta interactions with chondroitin sulfate-derived monosaccharides and disaccharides. implications for drug development.\nIn Alzheimer's disease, the major pathological features are diffuse and senile plaques that are primarily composed of the amyloid-beta (A beta) peptide. It has been proposed that proteoglycans and glycosaminoglycans (GAG) facilitate amyloid fibril formation and/or stabilize the plaque aggregates. To develop effective therapeutics based on A beta-GAG interactions, understanding the A beta binding motif on the GAG chain is imperative. Using electron microscopy, fluorescence spectroscopy, and competitive inhibition ELISAs, we have evaluated the ability of chondroitin sulfate-derived monosaccharides and disaccharides to induce the structural changes in A beta that are associated with GAG interactions. Our results demonstrate that the disaccharides GalNAc-4-sulfate(4S), Delta UA-GalNAc-6-sulfate(6S), and Delta UA-GalNAc-4,6-sulfate(4S,6S), the iduronic acid-2-sulfate analogues, and the monosaccharides d-GalNAc-4S, d-GalNAc-6S, and d-GalNAc-4S,6S, but not d-GalNAc, d-GlcNAc, or Delta UA-GalNAc, induce the fibrillar features of A beta-GAG interactions. The binding affinities of all chondroitin sulfate-derived saccharides mimic those of the intact GAG chains. The sulfated monosaccharides and disaccharides compete with the intact chondroitin sulfate and heparin GAGs for A beta binding, as illustrated by competitive inhibition ELISAs. Therefore, the development of therapeutics based on the model of A beta-chondroitin sulfate binding may lead to effective inhibitors of the GAG-induced amyloid formation that is observed in vitro."}

{"project":"GlyCosmos15-Glycan","denotations":[{"id":"T1","span":{"begin":31,"end":42},"obj":"Glycan"},{"id":"T2","span":{"begin":688,"end":699},"obj":"Glycan"},{"id":"T3","span":{"begin":883,"end":889},"obj":"Glycan"},{"id":"T4","span":{"begin":914,"end":920},"obj":"Glycan"},{"id":"T5","span":{"begin":949,"end":955},"obj":"Glycan"},{"id":"T6","span":{"begin":1041,"end":1047},"obj":"Glycan"},{"id":"T7","span":{"begin":1054,"end":1060},"obj":"Glycan"},{"id":"T8","span":{"begin":1071,"end":1077},"obj":"Glycan"},{"id":"T9","span":{"begin":1095,"end":1101},"obj":"Glycan"},{"id":"T10","span":{"begin":1125,"end":1131},"obj":"Glycan"},{"id":"T11","span":{"begin":1221,"end":1232},"obj":"Glycan"},{"id":"T12","span":{"begin":1370,"end":1381},"obj":"Glycan"},{"id":"T13","span":{"begin":1548,"end":1559},"obj":"Glycan"}],"attributes":[{"id":"A1","pred":"glycosmos_id","subj":"T1","obj":"https://glycosmos.org/glycans/show/G43702JT"},{"id":"A2","pred":"glycosmos_id","subj":"T2","obj":"https://glycosmos.org/glycans/show/G43702JT"},{"id":"A3","pred":"glycosmos_id","subj":"T3","obj":"https://glycosmos.org/glycans/show/G39738WL"},{"id":"A4","pred":"glycosmos_id","subj":"T4","obj":"https://glycosmos.org/glycans/show/G39738WL"},{"id":"A5","pred":"glycosmos_id","subj":"T5","obj":"https://glycosmos.org/glycans/show/G39738WL"},{"id":"A6","pred":"glycosmos_id","subj":"T6","obj":"https://glycosmos.org/glycans/show/G39738WL"},{"id":"A7","pred":"glycosmos_id","subj":"T7","obj":"https://glycosmos.org/glycans/show/G39738WL"},{"id":"A8","pred":"glycosmos_id","subj":"T8","obj":"https://glycosmos.org/glycans/show/G39738WL"},{"id":"A9","pred":"glycosmos_id","subj":"T9","obj":"https://glycosmos.org/glycans/show/G39738WL"},{"id":"A10","pred":"glycosmos_id","subj":"T10","obj":"https://glycosmos.org/glycans/show/G39738WL"},{"id":"A11","pred":"glycosmos_id","subj":"T11","obj":"https://glycosmos.org/glycans/show/G43702JT"},{"id":"A12","pred":"glycosmos_id","subj":"T12","obj":"https://glycosmos.org/glycans/show/G43702JT"},{"id":"A13","pred":"glycosmos_id","subj":"T13","obj":"https://glycosmos.org/glycans/show/G43702JT"},{"id":"A14","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G43702JT"},{"id":"A15","pred":"image","subj":"T2","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G43702JT"},{"id":"A16","pred":"image","subj":"T3","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G39738WL"},{"id":"A17","pred":"image","subj":"T4","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G39738WL"},{"id":"A18","pred":"image","subj":"T5","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G39738WL"},{"id":"A19","pred":"image","subj":"T6","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G39738WL"},{"id":"A20","pred":"image","subj":"T7","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G39738WL"},{"id":"A21","pred":"image","subj":"T8","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G39738WL"},{"id":"A22","pred":"image","subj":"T9","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G39738WL"},{"id":"A23","pred":"image","subj":"T10","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G39738WL"},{"id":"A24","pred":"image","subj":"T11","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G43702JT"},{"id":"A25","pred":"image","subj":"T12","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G43702JT"},{"id":"A26","pred":"image","subj":"T13","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G43702JT"}],"text":"Amyloid-beta interactions with chondroitin sulfate-derived monosaccharides and disaccharides. implications for drug development.\nIn Alzheimer's disease, the major pathological features are diffuse and senile plaques that are primarily composed of the amyloid-beta (A beta) peptide. It has been proposed that proteoglycans and glycosaminoglycans (GAG) facilitate amyloid fibril formation and/or stabilize the plaque aggregates. To develop effective therapeutics based on A beta-GAG interactions, understanding the A beta binding motif on the GAG chain is imperative. Using electron microscopy, fluorescence spectroscopy, and competitive inhibition ELISAs, we have evaluated the ability of chondroitin sulfate-derived monosaccharides and disaccharides to induce the structural changes in A beta that are associated with GAG interactions. Our results demonstrate that the disaccharides GalNAc-4-sulfate(4S), Delta UA-GalNAc-6-sulfate(6S), and Delta UA-GalNAc-4,6-sulfate(4S,6S), the iduronic acid-2-sulfate analogues, and the monosaccharides d-GalNAc-4S, d-GalNAc-6S, and d-GalNAc-4S,6S, but not d-GalNAc, d-GlcNAc, or Delta UA-GalNAc, induce the fibrillar features of A beta-GAG interactions. The binding affinities of all chondroitin sulfate-derived saccharides mimic those of the intact GAG chains. The sulfated monosaccharides and disaccharides compete with the intact chondroitin sulfate and heparin GAGs for A beta binding, as illustrated by competitive inhibition ELISAs. Therefore, the development of therapeutics based on the model of A beta-chondroitin sulfate binding may lead to effective inhibitors of the GAG-induced amyloid formation that is observed in vitro."}

{"project":"GlyCosmos15-GlycoEpitope","denotations":[{"id":"T1","span":{"begin":31,"end":42},"obj":"http://purl.jp/bio/12/glyco/glycan#Glycan_epitope"},{"id":"T2","span":{"begin":688,"end":699},"obj":"http://purl.jp/bio/12/glyco/glycan#Glycan_epitope"},{"id":"T3","span":{"begin":1221,"end":1232},"obj":"http://purl.jp/bio/12/glyco/glycan#Glycan_epitope"},{"id":"T4","span":{"begin":1370,"end":1381},"obj":"http://purl.jp/bio/12/glyco/glycan#Glycan_epitope"},{"id":"T5","span":{"begin":1548,"end":1559},"obj":"http://purl.jp/bio/12/glyco/glycan#Glycan_epitope"}],"attributes":[{"id":"A1","pred":"glycoepitope_id","subj":"T1","obj":"http://www.glycoepitope.jp/epitopes/EP0081"},{"id":"A2","pred":"glycoepitope_id","subj":"T2","obj":"http://www.glycoepitope.jp/epitopes/EP0081"},{"id":"A3","pred":"glycoepitope_id","subj":"T3","obj":"http://www.glycoepitope.jp/epitopes/EP0081"},{"id":"A4","pred":"glycoepitope_id","subj":"T4","obj":"http://www.glycoepitope.jp/epitopes/EP0081"},{"id":"A5","pred":"glycoepitope_id","subj":"T5","obj":"http://www.glycoepitope.jp/epitopes/EP0081"}],"text":"Amyloid-beta interactions with chondroitin sulfate-derived monosaccharides and disaccharides. implications for drug development.\nIn Alzheimer's disease, the major pathological features are diffuse and senile plaques that are primarily composed of the amyloid-beta (A beta) peptide. It has been proposed that proteoglycans and glycosaminoglycans (GAG) facilitate amyloid fibril formation and/or stabilize the plaque aggregates. To develop effective therapeutics based on A beta-GAG interactions, understanding the A beta binding motif on the GAG chain is imperative. Using electron microscopy, fluorescence spectroscopy, and competitive inhibition ELISAs, we have evaluated the ability of chondroitin sulfate-derived monosaccharides and disaccharides to induce the structural changes in A beta that are associated with GAG interactions. Our results demonstrate that the disaccharides GalNAc-4-sulfate(4S), Delta UA-GalNAc-6-sulfate(6S), and Delta UA-GalNAc-4,6-sulfate(4S,6S), the iduronic acid-2-sulfate analogues, and the monosaccharides d-GalNAc-4S, d-GalNAc-6S, and d-GalNAc-4S,6S, but not d-GalNAc, d-GlcNAc, or Delta UA-GalNAc, induce the fibrillar features of A beta-GAG interactions. The binding affinities of all chondroitin sulfate-derived saccharides mimic those of the intact GAG chains. The sulfated monosaccharides and disaccharides compete with the intact chondroitin sulfate and heparin GAGs for A beta binding, as illustrated by competitive inhibition ELISAs. Therefore, the development of therapeutics based on the model of A beta-chondroitin sulfate binding may lead to effective inhibitors of the GAG-induced amyloid formation that is observed in vitro."}

{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":370,"end":376},"obj":"Body_part"},{"id":"T2","span":{"begin":408,"end":414},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/GO_0099512"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0016482"}],"text":"Amyloid-beta interactions with chondroitin sulfate-derived monosaccharides and disaccharides. implications for drug development.\nIn Alzheimer's disease, the major pathological features are diffuse and senile plaques that are primarily composed of the amyloid-beta (A beta) peptide. It has been proposed that proteoglycans and glycosaminoglycans (GAG) facilitate amyloid fibril formation and/or stabilize the plaque aggregates. To develop effective therapeutics based on A beta-GAG interactions, understanding the A beta binding motif on the GAG chain is imperative. Using electron microscopy, fluorescence spectroscopy, and competitive inhibition ELISAs, we have evaluated the ability of chondroitin sulfate-derived monosaccharides and disaccharides to induce the structural changes in A beta that are associated with GAG interactions. Our results demonstrate that the disaccharides GalNAc-4-sulfate(4S), Delta UA-GalNAc-6-sulfate(6S), and Delta UA-GalNAc-4,6-sulfate(4S,6S), the iduronic acid-2-sulfate analogues, and the monosaccharides d-GalNAc-4S, d-GalNAc-6S, and d-GalNAc-4S,6S, but not d-GalNAc, d-GlcNAc, or Delta UA-GalNAc, induce the fibrillar features of A beta-GAG interactions. The binding affinities of all chondroitin sulfate-derived saccharides mimic those of the intact GAG chains. The sulfated monosaccharides and disaccharides compete with the intact chondroitin sulfate and heparin GAGs for A beta binding, as illustrated by competitive inhibition ELISAs. Therefore, the development of therapeutics based on the model of A beta-chondroitin sulfate binding may lead to effective inhibitors of the GAG-induced amyloid formation that is observed in vitro."}