PubMed:21823662 JSONTXT

{"project":"GlyCosmos15-Species","denotations":[{"id":"1791","span":{"begin":1133,"end":1136},"obj":"Species"}],"text":"A redesigned vancomycin engineered for dual D-Ala-D-ala And D-Ala-D-Lac binding exhibits potent antimicrobial activity against vancomycin-resistant bacteria.\nThe emergence of bacteria resistant to vancomycin, often the antibiotic of last resort, poses a major health problem. Vancomycin-resistant bacteria sense a glycopeptide antibiotic challenge and remodel their cell wall precursor peptidoglycan terminus from d-Ala-d-Ala to d-Ala-d-Lac, reducing the binding of vancomycin to its target 1000-fold and accounting for the loss in antimicrobial activity. Here, we report [Ψ[C(═NH)NH]Tpg(4)]vancomycin aglycon designed to exhibit the dual binding to d-Ala-d-Ala and d-Ala-d-Lac needed to reinstate activity against vancomycin-resistant bacteria. Its binding to a model d-Ala-d-Ala ligand was found to be only 2-fold less than vancomycin aglycon and this affinity was maintained with a model d-Ala-d-Lac ligand, representing a 600-fold increase relative to vancomycin aglycon. Accurately reflecting these binding characteristics, it exhibits potent antimicrobial activity against vancomycin-resistant bacteria (MIC = 0.31 μg/mL, VanA VRE). Thus, a complementary single atom exchange in the vancomycin core structure (O → NH) to counter the single atom exchange in the cell wall precursors of resistant bacteria (NH → O) reinstates potent antimicrobial activity and charts a rational path forward for the development of antibiotics for the treatment of vancomycin-resistant bacterial infections."}

{"project":"GlyCosmos15-Glycan","denotations":[{"id":"T1","span":{"begin":68,"end":71},"obj":"Glycan"},{"id":"T2","span":{"begin":437,"end":440},"obj":"Glycan"},{"id":"T3","span":{"begin":674,"end":677},"obj":"Glycan"},{"id":"T4","span":{"begin":899,"end":902},"obj":"Glycan"}],"attributes":[{"id":"A1","pred":"glycosmos_id","subj":"T1","obj":"https://glycosmos.org/glycans/show/ G84224TW"},{"id":"A5","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G84224TW"},{"id":"A2","pred":"glycosmos_id","subj":"T2","obj":"https://glycosmos.org/glycans/show/ G84224TW"},{"id":"A6","pred":"image","subj":"T2","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G84224TW"},{"id":"A3","pred":"glycosmos_id","subj":"T3","obj":"https://glycosmos.org/glycans/show/ G84224TW"},{"id":"A7","pred":"image","subj":"T3","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G84224TW"},{"id":"A4","pred":"glycosmos_id","subj":"T4","obj":"https://glycosmos.org/glycans/show/ G84224TW"},{"id":"A8","pred":"image","subj":"T4","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G84224TW"}],"text":"A redesigned vancomycin engineered for dual D-Ala-D-ala And D-Ala-D-Lac binding exhibits potent antimicrobial activity against vancomycin-resistant bacteria.\nThe emergence of bacteria resistant to vancomycin, often the antibiotic of last resort, poses a major health problem. Vancomycin-resistant bacteria sense a glycopeptide antibiotic challenge and remodel their cell wall precursor peptidoglycan terminus from d-Ala-d-Ala to d-Ala-d-Lac, reducing the binding of vancomycin to its target 1000-fold and accounting for the loss in antimicrobial activity. Here, we report [Ψ[C(═NH)NH]Tpg(4)]vancomycin aglycon designed to exhibit the dual binding to d-Ala-d-Ala and d-Ala-d-Lac needed to reinstate activity against vancomycin-resistant bacteria. Its binding to a model d-Ala-d-Ala ligand was found to be only 2-fold less than vancomycin aglycon and this affinity was maintained with a model d-Ala-d-Lac ligand, representing a 600-fold increase relative to vancomycin aglycon. Accurately reflecting these binding characteristics, it exhibits potent antimicrobial activity against vancomycin-resistant bacteria (MIC = 0.31 μg/mL, VanA VRE). Thus, a complementary single atom exchange in the vancomycin core structure (O → NH) to counter the single atom exchange in the cell wall precursors of resistant bacteria (NH → O) reinstates potent antimicrobial activity and charts a rational path forward for the development of antibiotics for the treatment of vancomycin-resistant bacterial infections."}

{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":1472,"end":1492},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0005113"}],"text":"A redesigned vancomycin engineered for dual D-Ala-D-ala And D-Ala-D-Lac binding exhibits potent antimicrobial activity against vancomycin-resistant bacteria.\nThe emergence of bacteria resistant to vancomycin, often the antibiotic of last resort, poses a major health problem. Vancomycin-resistant bacteria sense a glycopeptide antibiotic challenge and remodel their cell wall precursor peptidoglycan terminus from d-Ala-d-Ala to d-Ala-d-Lac, reducing the binding of vancomycin to its target 1000-fold and accounting for the loss in antimicrobial activity. Here, we report [Ψ[C(═NH)NH]Tpg(4)]vancomycin aglycon designed to exhibit the dual binding to d-Ala-d-Ala and d-Ala-d-Lac needed to reinstate activity against vancomycin-resistant bacteria. Its binding to a model d-Ala-d-Ala ligand was found to be only 2-fold less than vancomycin aglycon and this affinity was maintained with a model d-Ala-d-Lac ligand, representing a 600-fold increase relative to vancomycin aglycon. Accurately reflecting these binding characteristics, it exhibits potent antimicrobial activity against vancomycin-resistant bacteria (MIC = 0.31 μg/mL, VanA VRE). Thus, a complementary single atom exchange in the vancomycin core structure (O → NH) to counter the single atom exchange in the cell wall precursors of resistant bacteria (NH → O) reinstates potent antimicrobial activity and charts a rational path forward for the development of antibiotics for the treatment of vancomycin-resistant bacterial infections."}

{"project":"Glycan-GlyCosmos","denotations":[{"id":"T1","span":{"begin":68,"end":71},"obj":"Glycan"},{"id":"T2","span":{"begin":437,"end":440},"obj":"Glycan"},{"id":"T3","span":{"begin":674,"end":677},"obj":"Glycan"},{"id":"T4","span":{"begin":899,"end":902},"obj":"Glycan"}],"attributes":[{"id":"A1","pred":"glycosmos_id","subj":"T1","obj":"https://glycosmos.org/glycans/show/ G84224TW"},{"id":"A5","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G84224TW"},{"id":"A2","pred":"glycosmos_id","subj":"T2","obj":"https://glycosmos.org/glycans/show/ G84224TW"},{"id":"A6","pred":"image","subj":"T2","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G84224TW"},{"id":"A3","pred":"glycosmos_id","subj":"T3","obj":"https://glycosmos.org/glycans/show/ G84224TW"},{"id":"A7","pred":"image","subj":"T3","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G84224TW"},{"id":"A4","pred":"glycosmos_id","subj":"T4","obj":"https://glycosmos.org/glycans/show/ G84224TW"},{"id":"A8","pred":"image","subj":"T4","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G84224TW"}],"text":"A redesigned vancomycin engineered for dual D-Ala-D-ala And D-Ala-D-Lac binding exhibits potent antimicrobial activity against vancomycin-resistant bacteria.\nThe emergence of bacteria resistant to vancomycin, often the antibiotic of last resort, poses a major health problem. Vancomycin-resistant bacteria sense a glycopeptide antibiotic challenge and remodel their cell wall precursor peptidoglycan terminus from d-Ala-d-Ala to d-Ala-d-Lac, reducing the binding of vancomycin to its target 1000-fold and accounting for the loss in antimicrobial activity. Here, we report [Ψ[C(═NH)NH]Tpg(4)]vancomycin aglycon designed to exhibit the dual binding to d-Ala-d-Ala and d-Ala-d-Lac needed to reinstate activity against vancomycin-resistant bacteria. Its binding to a model d-Ala-d-Ala ligand was found to be only 2-fold less than vancomycin aglycon and this affinity was maintained with a model d-Ala-d-Lac ligand, representing a 600-fold increase relative to vancomycin aglycon. Accurately reflecting these binding characteristics, it exhibits potent antimicrobial activity against vancomycin-resistant bacteria (MIC = 0.31 μg/mL, VanA VRE). Thus, a complementary single atom exchange in the vancomycin core structure (O → NH) to counter the single atom exchange in the cell wall precursors of resistant bacteria (NH → O) reinstates potent antimicrobial activity and charts a rational path forward for the development of antibiotics for the treatment of vancomycin-resistant bacterial infections."}

{"project":"GlyCosmos15-MONDO","denotations":[{"id":"T1","span":{"begin":1472,"end":1492},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"MONDO:0005113"}],"namespaces":[{"prefix":"MONDO","uri":"http://purl.obolibrary.org/obo/MONDO_"}],"text":"A redesigned vancomycin engineered for dual D-Ala-D-ala And D-Ala-D-Lac binding exhibits potent antimicrobial activity against vancomycin-resistant bacteria.\nThe emergence of bacteria resistant to vancomycin, often the antibiotic of last resort, poses a major health problem. Vancomycin-resistant bacteria sense a glycopeptide antibiotic challenge and remodel their cell wall precursor peptidoglycan terminus from d-Ala-d-Ala to d-Ala-d-Lac, reducing the binding of vancomycin to its target 1000-fold and accounting for the loss in antimicrobial activity. Here, we report [Ψ[C(═NH)NH]Tpg(4)]vancomycin aglycon designed to exhibit the dual binding to d-Ala-d-Ala and d-Ala-d-Lac needed to reinstate activity against vancomycin-resistant bacteria. Its binding to a model d-Ala-d-Ala ligand was found to be only 2-fold less than vancomycin aglycon and this affinity was maintained with a model d-Ala-d-Lac ligand, representing a 600-fold increase relative to vancomycin aglycon. Accurately reflecting these binding characteristics, it exhibits potent antimicrobial activity against vancomycin-resistant bacteria (MIC = 0.31 μg/mL, VanA VRE). Thus, a complementary single atom exchange in the vancomycin core structure (O → NH) to counter the single atom exchange in the cell wall precursors of resistant bacteria (NH → O) reinstates potent antimicrobial activity and charts a rational path forward for the development of antibiotics for the treatment of vancomycin-resistant bacterial infections."}

{"project":"GlyCosmos15-UBERON","denotations":[{"id":"T1","span":{"begin":371,"end":375},"obj":"Body_part"},{"id":"T2","span":{"begin":1272,"end":1276},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0000060"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0000060"}],"text":"A redesigned vancomycin engineered for dual D-Ala-D-ala And D-Ala-D-Lac binding exhibits potent antimicrobial activity against vancomycin-resistant bacteria.\nThe emergence of bacteria resistant to vancomycin, often the antibiotic of last resort, poses a major health problem. Vancomycin-resistant bacteria sense a glycopeptide antibiotic challenge and remodel their cell wall precursor peptidoglycan terminus from d-Ala-d-Ala to d-Ala-d-Lac, reducing the binding of vancomycin to its target 1000-fold and accounting for the loss in antimicrobial activity. Here, we report [Ψ[C(═NH)NH]Tpg(4)]vancomycin aglycon designed to exhibit the dual binding to d-Ala-d-Ala and d-Ala-d-Lac needed to reinstate activity against vancomycin-resistant bacteria. Its binding to a model d-Ala-d-Ala ligand was found to be only 2-fold less than vancomycin aglycon and this affinity was maintained with a model d-Ala-d-Lac ligand, representing a 600-fold increase relative to vancomycin aglycon. Accurately reflecting these binding characteristics, it exhibits potent antimicrobial activity against vancomycin-resistant bacteria (MIC = 0.31 μg/mL, VanA VRE). Thus, a complementary single atom exchange in the vancomycin core structure (O → NH) to counter the single atom exchange in the cell wall precursors of resistant bacteria (NH → O) reinstates potent antimicrobial activity and charts a rational path forward for the development of antibiotics for the treatment of vancomycin-resistant bacterial infections."}

{"project":"GlyCosmos15-Sentences","blocks":[{"id":"T1","span":{"begin":0,"end":157},"obj":"Sentence"},{"id":"T2","span":{"begin":158,"end":275},"obj":"Sentence"},{"id":"T3","span":{"begin":276,"end":555},"obj":"Sentence"},{"id":"T4","span":{"begin":556,"end":745},"obj":"Sentence"},{"id":"T5","span":{"begin":746,"end":975},"obj":"Sentence"},{"id":"T6","span":{"begin":976,"end":1138},"obj":"Sentence"},{"id":"T7","span":{"begin":1139,"end":1493},"obj":"Sentence"}],"text":"A redesigned vancomycin engineered for dual D-Ala-D-ala And D-Ala-D-Lac binding exhibits potent antimicrobial activity against vancomycin-resistant bacteria.\nThe emergence of bacteria resistant to vancomycin, often the antibiotic of last resort, poses a major health problem. Vancomycin-resistant bacteria sense a glycopeptide antibiotic challenge and remodel their cell wall precursor peptidoglycan terminus from d-Ala-d-Ala to d-Ala-d-Lac, reducing the binding of vancomycin to its target 1000-fold and accounting for the loss in antimicrobial activity. Here, we report [Ψ[C(═NH)NH]Tpg(4)]vancomycin aglycon designed to exhibit the dual binding to d-Ala-d-Ala and d-Ala-d-Lac needed to reinstate activity against vancomycin-resistant bacteria. Its binding to a model d-Ala-d-Ala ligand was found to be only 2-fold less than vancomycin aglycon and this affinity was maintained with a model d-Ala-d-Lac ligand, representing a 600-fold increase relative to vancomycin aglycon. Accurately reflecting these binding characteristics, it exhibits potent antimicrobial activity against vancomycin-resistant bacteria (MIC = 0.31 μg/mL, VanA VRE). Thus, a complementary single atom exchange in the vancomycin core structure (O → NH) to counter the single atom exchange in the cell wall precursors of resistant bacteria (NH → O) reinstates potent antimicrobial activity and charts a rational path forward for the development of antibiotics for the treatment of vancomycin-resistant bacterial infections."}

{"project":"GlyCosmos15-NCBITAXON","denotations":[{"id":"T1","span":{"begin":148,"end":156},"obj":"OrganismTaxon"},{"id":"T3","span":{"begin":175,"end":183},"obj":"OrganismTaxon"},{"id":"T5","span":{"begin":297,"end":305},"obj":"OrganismTaxon"},{"id":"T7","span":{"begin":736,"end":744},"obj":"OrganismTaxon"},{"id":"T9","span":{"begin":1100,"end":1108},"obj":"OrganismTaxon"},{"id":"T11","span":{"begin":1301,"end":1309},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"2"},{"id":"A2","pred":"db_id","subj":"T1","obj":"629395"},{"id":"A3","pred":"db_id","subj":"T3","obj":"2"},{"id":"A4","pred":"db_id","subj":"T3","obj":"629395"},{"id":"A5","pred":"db_id","subj":"T5","obj":"2"},{"id":"A6","pred":"db_id","subj":"T5","obj":"629395"},{"id":"A7","pred":"db_id","subj":"T7","obj":"2"},{"id":"A8","pred":"db_id","subj":"T7","obj":"629395"},{"id":"A9","pred":"db_id","subj":"T9","obj":"2"},{"id":"A10","pred":"db_id","subj":"T9","obj":"629395"},{"id":"A11","pred":"db_id","subj":"T11","obj":"2"},{"id":"A12","pred":"db_id","subj":"T11","obj":"629395"}],"namespaces":[{"prefix":"_base","uri":"https://glycosmos.org/organisms/"}],"text":"A redesigned vancomycin engineered for dual D-Ala-D-ala And D-Ala-D-Lac binding exhibits potent antimicrobial activity against vancomycin-resistant bacteria.\nThe emergence of bacteria resistant to vancomycin, often the antibiotic of last resort, poses a major health problem. Vancomycin-resistant bacteria sense a glycopeptide antibiotic challenge and remodel their cell wall precursor peptidoglycan terminus from d-Ala-d-Ala to d-Ala-d-Lac, reducing the binding of vancomycin to its target 1000-fold and accounting for the loss in antimicrobial activity. Here, we report [Ψ[C(═NH)NH]Tpg(4)]vancomycin aglycon designed to exhibit the dual binding to d-Ala-d-Ala and d-Ala-d-Lac needed to reinstate activity against vancomycin-resistant bacteria. Its binding to a model d-Ala-d-Ala ligand was found to be only 2-fold less than vancomycin aglycon and this affinity was maintained with a model d-Ala-d-Lac ligand, representing a 600-fold increase relative to vancomycin aglycon. Accurately reflecting these binding characteristics, it exhibits potent antimicrobial activity against vancomycin-resistant bacteria (MIC = 0.31 μg/mL, VanA VRE). Thus, a complementary single atom exchange in the vancomycin core structure (O → NH) to counter the single atom exchange in the cell wall precursors of resistant bacteria (NH → O) reinstates potent antimicrobial activity and charts a rational path forward for the development of antibiotics for the treatment of vancomycin-resistant bacterial infections."}

{"project":"NCBITAXON","denotations":[{"id":"T1","span":{"begin":148,"end":156},"obj":"OrganismTaxon"},{"id":"T3","span":{"begin":175,"end":183},"obj":"OrganismTaxon"},{"id":"T5","span":{"begin":297,"end":305},"obj":"OrganismTaxon"},{"id":"T7","span":{"begin":736,"end":744},"obj":"OrganismTaxon"},{"id":"T9","span":{"begin":1100,"end":1108},"obj":"OrganismTaxon"},{"id":"T11","span":{"begin":1301,"end":1309},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"2"},{"id":"A2","pred":"db_id","subj":"T1","obj":"629395"},{"id":"A3","pred":"db_id","subj":"T3","obj":"2"},{"id":"A4","pred":"db_id","subj":"T3","obj":"629395"},{"id":"A5","pred":"db_id","subj":"T5","obj":"2"},{"id":"A6","pred":"db_id","subj":"T5","obj":"629395"},{"id":"A7","pred":"db_id","subj":"T7","obj":"2"},{"id":"A8","pred":"db_id","subj":"T7","obj":"629395"},{"id":"A9","pred":"db_id","subj":"T9","obj":"2"},{"id":"A10","pred":"db_id","subj":"T9","obj":"629395"},{"id":"A11","pred":"db_id","subj":"T11","obj":"2"},{"id":"A12","pred":"db_id","subj":"T11","obj":"629395"}],"text":"A redesigned vancomycin engineered for dual D-Ala-D-ala And D-Ala-D-Lac binding exhibits potent antimicrobial activity against vancomycin-resistant bacteria.\nThe emergence of bacteria resistant to vancomycin, often the antibiotic of last resort, poses a major health problem. Vancomycin-resistant bacteria sense a glycopeptide antibiotic challenge and remodel their cell wall precursor peptidoglycan terminus from d-Ala-d-Ala to d-Ala-d-Lac, reducing the binding of vancomycin to its target 1000-fold and accounting for the loss in antimicrobial activity. Here, we report [Ψ[C(═NH)NH]Tpg(4)]vancomycin aglycon designed to exhibit the dual binding to d-Ala-d-Ala and d-Ala-d-Lac needed to reinstate activity against vancomycin-resistant bacteria. Its binding to a model d-Ala-d-Ala ligand was found to be only 2-fold less than vancomycin aglycon and this affinity was maintained with a model d-Ala-d-Lac ligand, representing a 600-fold increase relative to vancomycin aglycon. Accurately reflecting these binding characteristics, it exhibits potent antimicrobial activity against vancomycin-resistant bacteria (MIC = 0.31 μg/mL, VanA VRE). Thus, a complementary single atom exchange in the vancomycin core structure (O → NH) to counter the single atom exchange in the cell wall precursors of resistant bacteria (NH → O) reinstates potent antimicrobial activity and charts a rational path forward for the development of antibiotics for the treatment of vancomycin-resistant bacterial infections."}

{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":371,"end":375},"obj":"Body_part"},{"id":"T2","span":{"begin":1272,"end":1276},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0000060"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0000060"}],"text":"A redesigned vancomycin engineered for dual D-Ala-D-ala And D-Ala-D-Lac binding exhibits potent antimicrobial activity against vancomycin-resistant bacteria.\nThe emergence of bacteria resistant to vancomycin, often the antibiotic of last resort, poses a major health problem. Vancomycin-resistant bacteria sense a glycopeptide antibiotic challenge and remodel their cell wall precursor peptidoglycan terminus from d-Ala-d-Ala to d-Ala-d-Lac, reducing the binding of vancomycin to its target 1000-fold and accounting for the loss in antimicrobial activity. Here, we report [Ψ[C(═NH)NH]Tpg(4)]vancomycin aglycon designed to exhibit the dual binding to d-Ala-d-Ala and d-Ala-d-Lac needed to reinstate activity against vancomycin-resistant bacteria. Its binding to a model d-Ala-d-Ala ligand was found to be only 2-fold less than vancomycin aglycon and this affinity was maintained with a model d-Ala-d-Lac ligand, representing a 600-fold increase relative to vancomycin aglycon. Accurately reflecting these binding characteristics, it exhibits potent antimicrobial activity against vancomycin-resistant bacteria (MIC = 0.31 μg/mL, VanA VRE). Thus, a complementary single atom exchange in the vancomycin core structure (O → NH) to counter the single atom exchange in the cell wall precursors of resistant bacteria (NH → O) reinstates potent antimicrobial activity and charts a rational path forward for the development of antibiotics for the treatment of vancomycin-resistant bacterial infections."}