کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1363140 981504 2009 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Vancomycin analogs: Seeking improved binding of d-Ala-d-Ala and d-Ala-d-Lac peptides by side-chain and backbone modifications
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Vancomycin analogs: Seeking improved binding of d-Ala-d-Ala and d-Ala-d-Lac peptides by side-chain and backbone modifications
چکیده انگلیسی

In order to seek vancomycin analogs with improved performance against VanA and VanB resistant bacterial strains, extensive computational investigations have been performed to examine the effects of side-chain and backbone modifications. Changes in binding affinities for tripeptide cell-wall precursor mimics, Ac2-l-Lys-d-Ala-d-Ala (3) and Ac2-l-Lys-d-Ala-d-Lac (4), with vancomycin analogs were computed with Monte Carlo/free energy perturbation (MC/FEP) calculations. Replacements of the 3-hydroxyl group in residue 7 with small alkyl or alkoxy groups, which improve contacts with the methyl side chain of the ligands’ d-Ala residue, are predicted to be the most promising to enhance binding for both ligands. The previously reported amine backbone modification as in 5 is shown to complement the hydrophobic modifications for binding monoacetylated tripeptides. In addition, replacement of the hydroxyl groups in residues 5 and 7 by fluorine is computed to have negligible impact on binding the tripeptides, though it may be pharmacologically advantageous.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 17, Issue 16, 15 August 2009, Pages 5874–5886
نویسندگان
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