PubMed:16079417 JSON TXT

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Glycan-Motif

{"project":"Glycan-Motif","denotations":[{"id":"T1","span":{"begin":12,"end":15},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T2","span":{"begin":439,"end":446},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T3","span":{"begin":448,"end":451},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T4","span":{"begin":460,"end":463},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T5","span":{"begin":492,"end":495},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T6","span":{"begin":525,"end":528},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T7","span":{"begin":541,"end":544},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T8","span":{"begin":573,"end":576},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T9","span":{"begin":676,"end":679},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T10","span":{"begin":1142,"end":1145},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T11","span":{"begin":1275,"end":1278},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T12","span":{"begin":1372,"end":1375},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T13","span":{"begin":1593,"end":1596},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T14","span":{"begin":1898,"end":1901},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"}],"text":"Hydrophobic Man-1-P derivatives correct abnormal glycosylation in Type I congenital disorder of glycosylation fibroblasts.\nPatients with Type I congenital disorders of glycosylation (CDG-I) make incomplete lipid-linked oligosaccharides (LLO). These glycans are poorly transferred to proteins resulting in unoccupied glycosylation sequons. Mutations in phosphomannomutase (PMM2) cause CDG-Ia by reducing the activity of PMM, which converts mannose (Man)-6-P to Man-1-P before formation of GDP-Man. These patients have reduced Man-1-P and GDP-Man. To replenish intracellular Man-1-P pools in CDG-Ia cells, we synthesized two hydrophobic, membrane permeable acylated versions of Man-1-P and determined their ability to normalize LLO size and N-glycosylation in CDG-Ia fibroblasts. Both compounds, compound I (diacetoxymethyl 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl phosphate) (C-I) and compound II (diacetoxymethyl 2,3,4,6-tetra-O-ethyloxycarbonyl-alpha-D-mannopyranosyl phosphate) (C-II), contain two acetoxymethyl (CH2OAc) groups O-linked to phosphorous. C-I contains acetyl esters and C-II contains ethylcarbonate (CO2Et) esters on the Man residue. Both C-I and C-II normalized truncated LLO, but C-II was about 2-fold more efficient than C-I. C-II replenished the GDP-Man pool in CDG-Ia cells and was more efficiently incorporated into glycoproteins than exogenous Man at low concentrations (25-75 mM). In a glycosylation assay of DNaseI in CDG-Ia cells, C-II restored glycosylation to control cell levels. C-II also corrected impaired LLO biosynthesis in cells from a Dolichol (Dol)-P-Man deficient patient (CDG-Ie) and partially corrected LLO in cells from an ALG12 mannosyltransferase-deficient patient (CDG-Ig), whereas cells from an ALG3-deficient patient (CDG-Id) and from an MPDU1-deficient patient (CDG-If) were not corrected. These results validate the general concept of using pro-Man-1-P substrates as potential therapeutics for CDG-I patients."}

GlyCosmos6-Glycan-Motif-Image

GlyCosmos6-Glycan-Motif-Structure

{"project":"GlyCosmos6-Glycan-Motif-Structure","denotations":[{"id":"T1","span":{"begin":439,"end":446},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"}],"text":"Hydrophobic Man-1-P derivatives correct abnormal glycosylation in Type I congenital disorder of glycosylation fibroblasts.\nPatients with Type I congenital disorders of glycosylation (CDG-I) make incomplete lipid-linked oligosaccharides (LLO). These glycans are poorly transferred to proteins resulting in unoccupied glycosylation sequons. Mutations in phosphomannomutase (PMM2) cause CDG-Ia by reducing the activity of PMM, which converts mannose (Man)-6-P to Man-1-P before formation of GDP-Man. These patients have reduced Man-1-P and GDP-Man. To replenish intracellular Man-1-P pools in CDG-Ia cells, we synthesized two hydrophobic, membrane permeable acylated versions of Man-1-P and determined their ability to normalize LLO size and N-glycosylation in CDG-Ia fibroblasts. Both compounds, compound I (diacetoxymethyl 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl phosphate) (C-I) and compound II (diacetoxymethyl 2,3,4,6-tetra-O-ethyloxycarbonyl-alpha-D-mannopyranosyl phosphate) (C-II), contain two acetoxymethyl (CH2OAc) groups O-linked to phosphorous. C-I contains acetyl esters and C-II contains ethylcarbonate (CO2Et) esters on the Man residue. Both C-I and C-II normalized truncated LLO, but C-II was about 2-fold more efficient than C-I. C-II replenished the GDP-Man pool in CDG-Ia cells and was more efficiently incorporated into glycoproteins than exogenous Man at low concentrations (25-75 mM). In a glycosylation assay of DNaseI in CDG-Ia cells, C-II restored glycosylation to control cell levels. C-II also corrected impaired LLO biosynthesis in cells from a Dolichol (Dol)-P-Man deficient patient (CDG-Ie) and partially corrected LLO in cells from an ALG12 mannosyltransferase-deficient patient (CDG-Ig), whereas cells from an ALG3-deficient patient (CDG-Id) and from an MPDU1-deficient patient (CDG-If) were not corrected. These results validate the general concept of using pro-Man-1-P substrates as potential therapeutics for CDG-I patients."}

GlycoBiology-GDGDB

uniprot-human

{"project":"uniprot-human","denotations":[{"id":"T1","span":{"begin":372,"end":376},"obj":"http://www.uniprot.org/uniprot/O15305"},{"id":"T2","span":{"begin":1669,"end":1674},"obj":"http://www.uniprot.org/uniprot/Q9BV10"},{"id":"T3","span":{"begin":1745,"end":1749},"obj":"http://www.uniprot.org/uniprot/Q92685"},{"id":"T4","span":{"begin":1789,"end":1794},"obj":"http://www.uniprot.org/uniprot/O75352"}],"text":"Hydrophobic Man-1-P derivatives correct abnormal glycosylation in Type I congenital disorder of glycosylation fibroblasts.\nPatients with Type I congenital disorders of glycosylation (CDG-I) make incomplete lipid-linked oligosaccharides (LLO). These glycans are poorly transferred to proteins resulting in unoccupied glycosylation sequons. Mutations in phosphomannomutase (PMM2) cause CDG-Ia by reducing the activity of PMM, which converts mannose (Man)-6-P to Man-1-P before formation of GDP-Man. These patients have reduced Man-1-P and GDP-Man. To replenish intracellular Man-1-P pools in CDG-Ia cells, we synthesized two hydrophobic, membrane permeable acylated versions of Man-1-P and determined their ability to normalize LLO size and N-glycosylation in CDG-Ia fibroblasts. Both compounds, compound I (diacetoxymethyl 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl phosphate) (C-I) and compound II (diacetoxymethyl 2,3,4,6-tetra-O-ethyloxycarbonyl-alpha-D-mannopyranosyl phosphate) (C-II), contain two acetoxymethyl (CH2OAc) groups O-linked to phosphorous. C-I contains acetyl esters and C-II contains ethylcarbonate (CO2Et) esters on the Man residue. Both C-I and C-II normalized truncated LLO, but C-II was about 2-fold more efficient than C-I. C-II replenished the GDP-Man pool in CDG-Ia cells and was more efficiently incorporated into glycoproteins than exogenous Man at low concentrations (25-75 mM). In a glycosylation assay of DNaseI in CDG-Ia cells, C-II restored glycosylation to control cell levels. C-II also corrected impaired LLO biosynthesis in cells from a Dolichol (Dol)-P-Man deficient patient (CDG-Ie) and partially corrected LLO in cells from an ALG12 mannosyltransferase-deficient patient (CDG-Ig), whereas cells from an ALG3-deficient patient (CDG-Id) and from an MPDU1-deficient patient (CDG-If) were not corrected. These results validate the general concept of using pro-Man-1-P substrates as potential therapeutics for CDG-I patients."}

uniprot-mouse

{"project":"uniprot-mouse","denotations":[{"id":"T1","span":{"begin":12,"end":15},"obj":"http://www.uniprot.org/uniprot/A2APV2"},{"id":"T2","span":{"begin":448,"end":451},"obj":"http://www.uniprot.org/uniprot/A2APV2"},{"id":"T3","span":{"begin":460,"end":463},"obj":"http://www.uniprot.org/uniprot/A2APV2"},{"id":"T4","span":{"begin":492,"end":495},"obj":"http://www.uniprot.org/uniprot/A2APV2"},{"id":"T5","span":{"begin":525,"end":528},"obj":"http://www.uniprot.org/uniprot/A2APV2"},{"id":"T6","span":{"begin":541,"end":544},"obj":"http://www.uniprot.org/uniprot/A2APV2"},{"id":"T7","span":{"begin":573,"end":576},"obj":"http://www.uniprot.org/uniprot/A2APV2"},{"id":"T8","span":{"begin":676,"end":679},"obj":"http://www.uniprot.org/uniprot/A2APV2"},{"id":"T9","span":{"begin":1142,"end":1145},"obj":"http://www.uniprot.org/uniprot/A2APV2"},{"id":"T10","span":{"begin":1275,"end":1278},"obj":"http://www.uniprot.org/uniprot/A2APV2"},{"id":"T11","span":{"begin":1372,"end":1375},"obj":"http://www.uniprot.org/uniprot/A2APV2"},{"id":"T12","span":{"begin":1593,"end":1596},"obj":"http://www.uniprot.org/uniprot/A2APV2"},{"id":"T13","span":{"begin":1898,"end":1901},"obj":"http://www.uniprot.org/uniprot/A2APV2"},{"id":"T14","span":{"begin":1894,"end":1897},"obj":"http://www.uniprot.org/uniprot/Q08761"}],"text":"Hydrophobic Man-1-P derivatives correct abnormal glycosylation in Type I congenital disorder of glycosylation fibroblasts.\nPatients with Type I congenital disorders of glycosylation (CDG-I) make incomplete lipid-linked oligosaccharides (LLO). These glycans are poorly transferred to proteins resulting in unoccupied glycosylation sequons. Mutations in phosphomannomutase (PMM2) cause CDG-Ia by reducing the activity of PMM, which converts mannose (Man)-6-P to Man-1-P before formation of GDP-Man. These patients have reduced Man-1-P and GDP-Man. To replenish intracellular Man-1-P pools in CDG-Ia cells, we synthesized two hydrophobic, membrane permeable acylated versions of Man-1-P and determined their ability to normalize LLO size and N-glycosylation in CDG-Ia fibroblasts. Both compounds, compound I (diacetoxymethyl 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl phosphate) (C-I) and compound II (diacetoxymethyl 2,3,4,6-tetra-O-ethyloxycarbonyl-alpha-D-mannopyranosyl phosphate) (C-II), contain two acetoxymethyl (CH2OAc) groups O-linked to phosphorous. C-I contains acetyl esters and C-II contains ethylcarbonate (CO2Et) esters on the Man residue. Both C-I and C-II normalized truncated LLO, but C-II was about 2-fold more efficient than C-I. C-II replenished the GDP-Man pool in CDG-Ia cells and was more efficiently incorporated into glycoproteins than exogenous Man at low concentrations (25-75 mM). In a glycosylation assay of DNaseI in CDG-Ia cells, C-II restored glycosylation to control cell levels. C-II also corrected impaired LLO biosynthesis in cells from a Dolichol (Dol)-P-Man deficient patient (CDG-Ie) and partially corrected LLO in cells from an ALG12 mannosyltransferase-deficient patient (CDG-Ig), whereas cells from an ALG3-deficient patient (CDG-Id) and from an MPDU1-deficient patient (CDG-If) were not corrected. These results validate the general concept of using pro-Man-1-P substrates as potential therapeutics for CDG-I patients."}

GlycoBiology-NCBITAXON

{"project":"GlycoBiology-NCBITAXON","denotations":[{"id":"T1","span":{"begin":597,"end":602},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T2","span":{"begin":830,"end":835},"obj":"http://purl.bioontology.org/ontology/NCBITAXON/85284"},{"id":"T3","span":{"begin":830,"end":835},"obj":"http://purl.bioontology.org/ontology/NCBITAXON/1310384"},{"id":"T4","span":{"begin":926,"end":931},"obj":"http://purl.bioontology.org/ontology/NCBITAXON/1310384"},{"id":"T5","span":{"begin":926,"end":931},"obj":"http://purl.bioontology.org/ontology/NCBITAXON/85284"},{"id":"T6","span":{"begin":1028,"end":1034},"obj":"http://purl.bioontology.org/ontology/STY/T096"},{"id":"T7","span":{"begin":1294,"end":1299},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T8","span":{"begin":1455,"end":1460},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T9","span":{"begin":1563,"end":1568},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T10","span":{"begin":1655,"end":1660},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T11","span":{"begin":1731,"end":1736},"obj":"http://purl.bioontology.org/ontology/STY/T025"}],"text":"Hydrophobic Man-1-P derivatives correct abnormal glycosylation in Type I congenital disorder of glycosylation fibroblasts.\nPatients with Type I congenital disorders of glycosylation (CDG-I) make incomplete lipid-linked oligosaccharides (LLO). These glycans are poorly transferred to proteins resulting in unoccupied glycosylation sequons. Mutations in phosphomannomutase (PMM2) cause CDG-Ia by reducing the activity of PMM, which converts mannose (Man)-6-P to Man-1-P before formation of GDP-Man. These patients have reduced Man-1-P and GDP-Man. To replenish intracellular Man-1-P pools in CDG-Ia cells, we synthesized two hydrophobic, membrane permeable acylated versions of Man-1-P and determined their ability to normalize LLO size and N-glycosylation in CDG-Ia fibroblasts. Both compounds, compound I (diacetoxymethyl 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl phosphate) (C-I) and compound II (diacetoxymethyl 2,3,4,6-tetra-O-ethyloxycarbonyl-alpha-D-mannopyranosyl phosphate) (C-II), contain two acetoxymethyl (CH2OAc) groups O-linked to phosphorous. C-I contains acetyl esters and C-II contains ethylcarbonate (CO2Et) esters on the Man residue. Both C-I and C-II normalized truncated LLO, but C-II was about 2-fold more efficient than C-I. C-II replenished the GDP-Man pool in CDG-Ia cells and was more efficiently incorporated into glycoproteins than exogenous Man at low concentrations (25-75 mM). In a glycosylation assay of DNaseI in CDG-Ia cells, C-II restored glycosylation to control cell levels. C-II also corrected impaired LLO biosynthesis in cells from a Dolichol (Dol)-P-Man deficient patient (CDG-Ie) and partially corrected LLO in cells from an ALG12 mannosyltransferase-deficient patient (CDG-Ig), whereas cells from an ALG3-deficient patient (CDG-Id) and from an MPDU1-deficient patient (CDG-If) were not corrected. These results validate the general concept of using pro-Man-1-P substrates as potential therapeutics for CDG-I patients."}

GO-BP

{"project":"GO-BP","denotations":[{"id":"T1","span":{"begin":49,"end":62},"obj":"http://purl.obolibrary.org/obo/GO_0070085"},{"id":"T2","span":{"begin":96,"end":109},"obj":"http://purl.obolibrary.org/obo/GO_0070085"},{"id":"T3","span":{"begin":168,"end":181},"obj":"http://purl.obolibrary.org/obo/GO_0070085"},{"id":"T4","span":{"begin":316,"end":329},"obj":"http://purl.obolibrary.org/obo/GO_0070085"},{"id":"T5","span":{"begin":741,"end":754},"obj":"http://purl.obolibrary.org/obo/GO_0070085"},{"id":"T6","span":{"begin":1415,"end":1428},"obj":"http://purl.obolibrary.org/obo/GO_0070085"},{"id":"T7","span":{"begin":1476,"end":1489},"obj":"http://purl.obolibrary.org/obo/GO_0070085"},{"id":"T8","span":{"begin":475,"end":484},"obj":"http://purl.obolibrary.org/obo/GO_0009058"},{"id":"T9","span":{"begin":475,"end":491},"obj":"http://purl.obolibrary.org/obo/GO_0046711"},{"id":"T10","span":{"begin":1362,"end":1371},"obj":"http://purl.obolibrary.org/obo/GO_0042638"},{"id":"T11","span":{"begin":1547,"end":1559},"obj":"http://purl.obolibrary.org/obo/GO_0009058"}],"text":"Hydrophobic Man-1-P derivatives correct abnormal glycosylation in Type I congenital disorder of glycosylation fibroblasts.\nPatients with Type I congenital disorders of glycosylation (CDG-I) make incomplete lipid-linked oligosaccharides (LLO). These glycans are poorly transferred to proteins resulting in unoccupied glycosylation sequons. Mutations in phosphomannomutase (PMM2) cause CDG-Ia by reducing the activity of PMM, which converts mannose (Man)-6-P to Man-1-P before formation of GDP-Man. These patients have reduced Man-1-P and GDP-Man. To replenish intracellular Man-1-P pools in CDG-Ia cells, we synthesized two hydrophobic, membrane permeable acylated versions of Man-1-P and determined their ability to normalize LLO size and N-glycosylation in CDG-Ia fibroblasts. Both compounds, compound I (diacetoxymethyl 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl phosphate) (C-I) and compound II (diacetoxymethyl 2,3,4,6-tetra-O-ethyloxycarbonyl-alpha-D-mannopyranosyl phosphate) (C-II), contain two acetoxymethyl (CH2OAc) groups O-linked to phosphorous. C-I contains acetyl esters and C-II contains ethylcarbonate (CO2Et) esters on the Man residue. Both C-I and C-II normalized truncated LLO, but C-II was about 2-fold more efficient than C-I. C-II replenished the GDP-Man pool in CDG-Ia cells and was more efficiently incorporated into glycoproteins than exogenous Man at low concentrations (25-75 mM). In a glycosylation assay of DNaseI in CDG-Ia cells, C-II restored glycosylation to control cell levels. C-II also corrected impaired LLO biosynthesis in cells from a Dolichol (Dol)-P-Man deficient patient (CDG-Ie) and partially corrected LLO in cells from an ALG12 mannosyltransferase-deficient patient (CDG-Ig), whereas cells from an ALG3-deficient patient (CDG-Id) and from an MPDU1-deficient patient (CDG-If) were not corrected. These results validate the general concept of using pro-Man-1-P substrates as potential therapeutics for CDG-I patients."}

GO-CC

{"project":"GO-CC","denotations":[{"id":"T1","span":{"begin":559,"end":572},"obj":"http://purl.obolibrary.org/obo/GO_0005622"},{"id":"T2","span":{"begin":597,"end":602},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T3","span":{"begin":1294,"end":1299},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T4","span":{"begin":1455,"end":1460},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T5","span":{"begin":1563,"end":1568},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T6","span":{"begin":1655,"end":1660},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T7","span":{"begin":1501,"end":1505},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T8","span":{"begin":636,"end":644},"obj":"http://purl.obolibrary.org/obo/GO_0016020"}],"text":"Hydrophobic Man-1-P derivatives correct abnormal glycosylation in Type I congenital disorder of glycosylation fibroblasts.\nPatients with Type I congenital disorders of glycosylation (CDG-I) make incomplete lipid-linked oligosaccharides (LLO). These glycans are poorly transferred to proteins resulting in unoccupied glycosylation sequons. Mutations in phosphomannomutase (PMM2) cause CDG-Ia by reducing the activity of PMM, which converts mannose (Man)-6-P to Man-1-P before formation of GDP-Man. These patients have reduced Man-1-P and GDP-Man. To replenish intracellular Man-1-P pools in CDG-Ia cells, we synthesized two hydrophobic, membrane permeable acylated versions of Man-1-P and determined their ability to normalize LLO size and N-glycosylation in CDG-Ia fibroblasts. Both compounds, compound I (diacetoxymethyl 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl phosphate) (C-I) and compound II (diacetoxymethyl 2,3,4,6-tetra-O-ethyloxycarbonyl-alpha-D-mannopyranosyl phosphate) (C-II), contain two acetoxymethyl (CH2OAc) groups O-linked to phosphorous. C-I contains acetyl esters and C-II contains ethylcarbonate (CO2Et) esters on the Man residue. Both C-I and C-II normalized truncated LLO, but C-II was about 2-fold more efficient than C-I. C-II replenished the GDP-Man pool in CDG-Ia cells and was more efficiently incorporated into glycoproteins than exogenous Man at low concentrations (25-75 mM). In a glycosylation assay of DNaseI in CDG-Ia cells, C-II restored glycosylation to control cell levels. C-II also corrected impaired LLO biosynthesis in cells from a Dolichol (Dol)-P-Man deficient patient (CDG-Ie) and partially corrected LLO in cells from an ALG12 mannosyltransferase-deficient patient (CDG-Ig), whereas cells from an ALG3-deficient patient (CDG-Id) and from an MPDU1-deficient patient (CDG-If) were not corrected. These results validate the general concept of using pro-Man-1-P substrates as potential therapeutics for CDG-I patients."}

DisGeNET5_gene_disease

sentences

Lectin

{"project":"Lectin","denotations":[{"id":"Lectin_T1","span":{"begin":12,"end":15},"obj":"https://acgg.asia/db/lfdb/LfDB0217"},{"id":"Lectin_T2","span":{"begin":448,"end":451},"obj":"https://acgg.asia/db/lfdb/LfDB0217"},{"id":"Lectin_T3","span":{"begin":460,"end":463},"obj":"https://acgg.asia/db/lfdb/LfDB0217"},{"id":"Lectin_T4","span":{"begin":492,"end":495},"obj":"https://acgg.asia/db/lfdb/LfDB0217"},{"id":"Lectin_T5","span":{"begin":525,"end":528},"obj":"https://acgg.asia/db/lfdb/LfDB0217"},{"id":"Lectin_T6","span":{"begin":541,"end":544},"obj":"https://acgg.asia/db/lfdb/LfDB0217"},{"id":"Lectin_T7","span":{"begin":573,"end":576},"obj":"https://acgg.asia/db/lfdb/LfDB0217"},{"id":"Lectin_T8","span":{"begin":676,"end":679},"obj":"https://acgg.asia/db/lfdb/LfDB0217"},{"id":"Lectin_T9","span":{"begin":1142,"end":1145},"obj":"https://acgg.asia/db/lfdb/LfDB0217"},{"id":"Lectin_T10","span":{"begin":1275,"end":1278},"obj":"https://acgg.asia/db/lfdb/LfDB0217"},{"id":"Lectin_T11","span":{"begin":1372,"end":1375},"obj":"https://acgg.asia/db/lfdb/LfDB0217"},{"id":"Lectin_T12","span":{"begin":1593,"end":1596},"obj":"https://acgg.asia/db/lfdb/LfDB0217"},{"id":"Lectin_T13","span":{"begin":1898,"end":1901},"obj":"https://acgg.asia/db/lfdb/LfDB0217"}],"text":"Hydrophobic Man-1-P derivatives correct abnormal glycosylation in Type I congenital disorder of glycosylation fibroblasts.\nPatients with Type I congenital disorders of glycosylation (CDG-I) make incomplete lipid-linked oligosaccharides (LLO). These glycans are poorly transferred to proteins resulting in unoccupied glycosylation sequons. Mutations in phosphomannomutase (PMM2) cause CDG-Ia by reducing the activity of PMM, which converts mannose (Man)-6-P to Man-1-P before formation of GDP-Man. These patients have reduced Man-1-P and GDP-Man. To replenish intracellular Man-1-P pools in CDG-Ia cells, we synthesized two hydrophobic, membrane permeable acylated versions of Man-1-P and determined their ability to normalize LLO size and N-glycosylation in CDG-Ia fibroblasts. Both compounds, compound I (diacetoxymethyl 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl phosphate) (C-I) and compound II (diacetoxymethyl 2,3,4,6-tetra-O-ethyloxycarbonyl-alpha-D-mannopyranosyl phosphate) (C-II), contain two acetoxymethyl (CH2OAc) groups O-linked to phosphorous. C-I contains acetyl esters and C-II contains ethylcarbonate (CO2Et) esters on the Man residue. Both C-I and C-II normalized truncated LLO, but C-II was about 2-fold more efficient than C-I. C-II replenished the GDP-Man pool in CDG-Ia cells and was more efficiently incorporated into glycoproteins than exogenous Man at low concentrations (25-75 mM). In a glycosylation assay of DNaseI in CDG-Ia cells, C-II restored glycosylation to control cell levels. C-II also corrected impaired LLO biosynthesis in cells from a Dolichol (Dol)-P-Man deficient patient (CDG-Ie) and partially corrected LLO in cells from an ALG12 mannosyltransferase-deficient patient (CDG-Ig), whereas cells from an ALG3-deficient patient (CDG-Id) and from an MPDU1-deficient patient (CDG-If) were not corrected. These results validate the general concept of using pro-Man-1-P substrates as potential therapeutics for CDG-I patients."}

GlyTouCan-IUPAC

DisGeNET

{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":676,"end":681},"obj":"gene:23592"},{"id":"T1","span":{"begin":758,"end":764},"obj":"disease:C0349653"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"text":"Hydrophobic Man-1-P derivatives correct abnormal glycosylation in Type I congenital disorder of glycosylation fibroblasts.\nPatients with Type I congenital disorders of glycosylation (CDG-I) make incomplete lipid-linked oligosaccharides (LLO). These glycans are poorly transferred to proteins resulting in unoccupied glycosylation sequons. Mutations in phosphomannomutase (PMM2) cause CDG-Ia by reducing the activity of PMM, which converts mannose (Man)-6-P to Man-1-P before formation of GDP-Man. These patients have reduced Man-1-P and GDP-Man. To replenish intracellular Man-1-P pools in CDG-Ia cells, we synthesized two hydrophobic, membrane permeable acylated versions of Man-1-P and determined their ability to normalize LLO size and N-glycosylation in CDG-Ia fibroblasts. Both compounds, compound I (diacetoxymethyl 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl phosphate) (C-I) and compound II (diacetoxymethyl 2,3,4,6-tetra-O-ethyloxycarbonyl-alpha-D-mannopyranosyl phosphate) (C-II), contain two acetoxymethyl (CH2OAc) groups O-linked to phosphorous. C-I contains acetyl esters and C-II contains ethylcarbonate (CO2Et) esters on the Man residue. Both C-I and C-II normalized truncated LLO, but C-II was about 2-fold more efficient than C-I. C-II replenished the GDP-Man pool in CDG-Ia cells and was more efficiently incorporated into glycoproteins than exogenous Man at low concentrations (25-75 mM). In a glycosylation assay of DNaseI in CDG-Ia cells, C-II restored glycosylation to control cell levels. C-II also corrected impaired LLO biosynthesis in cells from a Dolichol (Dol)-P-Man deficient patient (CDG-Ie) and partially corrected LLO in cells from an ALG12 mannosyltransferase-deficient patient (CDG-Ig), whereas cells from an ALG3-deficient patient (CDG-Id) and from an MPDU1-deficient patient (CDG-If) were not corrected. These results validate the general concept of using pro-Man-1-P substrates as potential therapeutics for CDG-I patients."}

mondo_disease

HP-phenotype

{"project":"HP-phenotype","denotations":[{"id":"T1","span":{"begin":40,"end":62},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0012345"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}],"text":"Hydrophobic Man-1-P derivatives correct abnormal glycosylation in Type I congenital disorder of glycosylation fibroblasts.\nPatients with Type I congenital disorders of glycosylation (CDG-I) make incomplete lipid-linked oligosaccharides (LLO). These glycans are poorly transferred to proteins resulting in unoccupied glycosylation sequons. Mutations in phosphomannomutase (PMM2) cause CDG-Ia by reducing the activity of PMM, which converts mannose (Man)-6-P to Man-1-P before formation of GDP-Man. These patients have reduced Man-1-P and GDP-Man. To replenish intracellular Man-1-P pools in CDG-Ia cells, we synthesized two hydrophobic, membrane permeable acylated versions of Man-1-P and determined their ability to normalize LLO size and N-glycosylation in CDG-Ia fibroblasts. Both compounds, compound I (diacetoxymethyl 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl phosphate) (C-I) and compound II (diacetoxymethyl 2,3,4,6-tetra-O-ethyloxycarbonyl-alpha-D-mannopyranosyl phosphate) (C-II), contain two acetoxymethyl (CH2OAc) groups O-linked to phosphorous. C-I contains acetyl esters and C-II contains ethylcarbonate (CO2Et) esters on the Man residue. Both C-I and C-II normalized truncated LLO, but C-II was about 2-fold more efficient than C-I. C-II replenished the GDP-Man pool in CDG-Ia cells and was more efficiently incorporated into glycoproteins than exogenous Man at low concentrations (25-75 mM). In a glycosylation assay of DNaseI in CDG-Ia cells, C-II restored glycosylation to control cell levels. C-II also corrected impaired LLO biosynthesis in cells from a Dolichol (Dol)-P-Man deficient patient (CDG-Ie) and partially corrected LLO in cells from an ALG12 mannosyltransferase-deficient patient (CDG-Ig), whereas cells from an ALG3-deficient patient (CDG-Id) and from an MPDU1-deficient patient (CDG-If) were not corrected. These results validate the general concept of using pro-Man-1-P substrates as potential therapeutics for CDG-I patients."}

NCBITAXON

{"project":"NCBITAXON","denotations":[{"id":"T1","span":{"begin":830,"end":837},"obj":"OrganismTaxon"},{"id":"T2","span":{"begin":926,"end":933},"obj":"OrganismTaxon"},{"id":"T3","span":{"begin":1607,"end":1614},"obj":"OrganismTaxon"},{"id":"T4","span":{"begin":1705,"end":1712},"obj":"OrganismTaxon"},{"id":"T5","span":{"begin":1760,"end":1767},"obj":"OrganismTaxon"},{"id":"T6","span":{"begin":1805,"end":1812},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"100829"},{"id":"A2","pred":"db_id","subj":"T2","obj":"100829"},{"id":"A3","pred":"db_id","subj":"T3","obj":"9606"},{"id":"A4","pred":"db_id","subj":"T4","obj":"9606"},{"id":"A5","pred":"db_id","subj":"T5","obj":"9606"},{"id":"A6","pred":"db_id","subj":"T6","obj":"9606"}],"text":"Hydrophobic Man-1-P derivatives correct abnormal glycosylation in Type I congenital disorder of glycosylation fibroblasts.\nPatients with Type I congenital disorders of glycosylation (CDG-I) make incomplete lipid-linked oligosaccharides (LLO). These glycans are poorly transferred to proteins resulting in unoccupied glycosylation sequons. Mutations in phosphomannomutase (PMM2) cause CDG-Ia by reducing the activity of PMM, which converts mannose (Man)-6-P to Man-1-P before formation of GDP-Man. These patients have reduced Man-1-P and GDP-Man. To replenish intracellular Man-1-P pools in CDG-Ia cells, we synthesized two hydrophobic, membrane permeable acylated versions of Man-1-P and determined their ability to normalize LLO size and N-glycosylation in CDG-Ia fibroblasts. Both compounds, compound I (diacetoxymethyl 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl phosphate) (C-I) and compound II (diacetoxymethyl 2,3,4,6-tetra-O-ethyloxycarbonyl-alpha-D-mannopyranosyl phosphate) (C-II), contain two acetoxymethyl (CH2OAc) groups O-linked to phosphorous. C-I contains acetyl esters and C-II contains ethylcarbonate (CO2Et) esters on the Man residue. Both C-I and C-II normalized truncated LLO, but C-II was about 2-fold more efficient than C-I. C-II replenished the GDP-Man pool in CDG-Ia cells and was more efficiently incorporated into glycoproteins than exogenous Man at low concentrations (25-75 mM). In a glycosylation assay of DNaseI in CDG-Ia cells, C-II restored glycosylation to control cell levels. C-II also corrected impaired LLO biosynthesis in cells from a Dolichol (Dol)-P-Man deficient patient (CDG-Ie) and partially corrected LLO in cells from an ALG12 mannosyltransferase-deficient patient (CDG-Ig), whereas cells from an ALG3-deficient patient (CDG-Id) and from an MPDU1-deficient patient (CDG-If) were not corrected. These results validate the general concept of using pro-Man-1-P substrates as potential therapeutics for CDG-I patients."}

Anatomy-UBERON

{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":110,"end":121},"obj":"Body_part"},{"id":"T2","span":{"begin":559,"end":572},"obj":"Body_part"},{"id":"T3","span":{"begin":636,"end":644},"obj":"Body_part"},{"id":"T6","span":{"begin":765,"end":776},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL_0000057"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/GO_0005622"},{"id":"A3","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/GO_0016020"},{"id":"A4","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/UBERON_0000094"},{"id":"A5","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/UBERON_0000158"},{"id":"A6","pred":"uberon_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/CL_0000057"}],"text":"Hydrophobic Man-1-P derivatives correct abnormal glycosylation in Type I congenital disorder of glycosylation fibroblasts.\nPatients with Type I congenital disorders of glycosylation (CDG-I) make incomplete lipid-linked oligosaccharides (LLO). These glycans are poorly transferred to proteins resulting in unoccupied glycosylation sequons. Mutations in phosphomannomutase (PMM2) cause CDG-Ia by reducing the activity of PMM, which converts mannose (Man)-6-P to Man-1-P before formation of GDP-Man. These patients have reduced Man-1-P and GDP-Man. To replenish intracellular Man-1-P pools in CDG-Ia cells, we synthesized two hydrophobic, membrane permeable acylated versions of Man-1-P and determined their ability to normalize LLO size and N-glycosylation in CDG-Ia fibroblasts. Both compounds, compound I (diacetoxymethyl 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl phosphate) (C-I) and compound II (diacetoxymethyl 2,3,4,6-tetra-O-ethyloxycarbonyl-alpha-D-mannopyranosyl phosphate) (C-II), contain two acetoxymethyl (CH2OAc) groups O-linked to phosphorous. C-I contains acetyl esters and C-II contains ethylcarbonate (CO2Et) esters on the Man residue. Both C-I and C-II normalized truncated LLO, but C-II was about 2-fold more efficient than C-I. C-II replenished the GDP-Man pool in CDG-Ia cells and was more efficiently incorporated into glycoproteins than exogenous Man at low concentrations (25-75 mM). In a glycosylation assay of DNaseI in CDG-Ia cells, C-II restored glycosylation to control cell levels. C-II also corrected impaired LLO biosynthesis in cells from a Dolichol (Dol)-P-Man deficient patient (CDG-Ie) and partially corrected LLO in cells from an ALG12 mannosyltransferase-deficient patient (CDG-Ig), whereas cells from an ALG3-deficient patient (CDG-Id) and from an MPDU1-deficient patient (CDG-If) were not corrected. These results validate the general concept of using pro-Man-1-P substrates as potential therapeutics for CDG-I patients."}

CL-cell

{"project":"CL-cell","denotations":[{"id":"T1","span":{"begin":66,"end":72},"obj":"Cell"},{"id":"T3","span":{"begin":110,"end":121},"obj":"Cell"},{"id":"T4","span":{"begin":137,"end":143},"obj":"Cell"},{"id":"T6","span":{"begin":765,"end":776},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0004120"},{"id":"A2","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0004138"},{"id":"A3","pred":"cl_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CL:0000057"},{"id":"A4","pred":"cl_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/CL:0004120"},{"id":"A5","pred":"cl_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/CL:0004138"},{"id":"A6","pred":"cl_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/CL:0000057"}],"text":"Hydrophobic Man-1-P derivatives correct abnormal glycosylation in Type I congenital disorder of glycosylation fibroblasts.\nPatients with Type I congenital disorders of glycosylation (CDG-I) make incomplete lipid-linked oligosaccharides (LLO). These glycans are poorly transferred to proteins resulting in unoccupied glycosylation sequons. Mutations in phosphomannomutase (PMM2) cause CDG-Ia by reducing the activity of PMM, which converts mannose (Man)-6-P to Man-1-P before formation of GDP-Man. These patients have reduced Man-1-P and GDP-Man. To replenish intracellular Man-1-P pools in CDG-Ia cells, we synthesized two hydrophobic, membrane permeable acylated versions of Man-1-P and determined their ability to normalize LLO size and N-glycosylation in CDG-Ia fibroblasts. Both compounds, compound I (diacetoxymethyl 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl phosphate) (C-I) and compound II (diacetoxymethyl 2,3,4,6-tetra-O-ethyloxycarbonyl-alpha-D-mannopyranosyl phosphate) (C-II), contain two acetoxymethyl (CH2OAc) groups O-linked to phosphorous. C-I contains acetyl esters and C-II contains ethylcarbonate (CO2Et) esters on the Man residue. Both C-I and C-II normalized truncated LLO, but C-II was about 2-fold more efficient than C-I. C-II replenished the GDP-Man pool in CDG-Ia cells and was more efficiently incorporated into glycoproteins than exogenous Man at low concentrations (25-75 mM). In a glycosylation assay of DNaseI in CDG-Ia cells, C-II restored glycosylation to control cell levels. C-II also corrected impaired LLO biosynthesis in cells from a Dolichol (Dol)-P-Man deficient patient (CDG-Ie) and partially corrected LLO in cells from an ALG12 mannosyltransferase-deficient patient (CDG-Ig), whereas cells from an ALG3-deficient patient (CDG-Id) and from an MPDU1-deficient patient (CDG-If) were not corrected. These results validate the general concept of using pro-Man-1-P substrates as potential therapeutics for CDG-I patients."}