Unknown

Dataset Information

0

Vancomycin resistance: modeling backbone variants with D-Ala-D-Ala and D-Ala-D-Lac peptides.


ABSTRACT: To seek vancomycin analogs with broader antibacterial activity, effects of backbone modifications for the agylcon 2 on binding with D-Ala-D-Ala- and D-Ala-D-Lac-containing peptides were investigated by Monte Carlo/free energy perturbation (MC/FEP) calculations. The experimental trend in binding affinities for 2 with three tripeptides was well reproduced. Possible modifications of the peptide bond between residues 4 and 5 were then considered, specifically for conversion of the OCNH linkage to CH(2)NH(2)(+) (6), FCCH (7), HCCH (8), and HNCO (9). The MC/FEP results did not yield binding improvements for 7, 8, and 9, though the fluorovinyl replacement is relatively benign. The previously reported analog 6 remains as the only variant that exhibits improved affinity for the D-Ala-D-Lac sequence and acceptable affinity for the D-Ala-D-Ala sequence.

SUBMITTER: Leung SS 

PROVIDER: S-EPMC2702131 | BioStudies | 2009-01-01

REPOSITORIES: biostudies

Similar Datasets

2009-01-01 | S-EPMC2892990 | BioStudies
2011-01-01 | S-EPMC3164945 | BioStudies
2006-01-01 | S-EPMC2586002 | BioStudies
2017-01-01 | S-EPMC6906607 | BioStudies
2014-01-01 | S-EPMC4229326 | BioStudies
2016-01-01 | S-EPMC5039762 | BioStudies
2013-01-01 | S-EPMC3754309 | BioStudies
2012-01-01 | S-EPMC3262083 | BioStudies
2012-01-01 | S-EPMC3488035 | BioStudies
1000-01-01 | S-EPMC3181209 | BioStudies