Partitioning the loss in vancomycin binding affinity for D-Ala-D-Lac into lost H-bond and repulsive lone pair contributions.

Partitioning the loss in vancomycin binding affinity for D-Ala-D-Lac into lost H-bond and repulsive lone pair contributions. Research Abstract Details 

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Partitioning the loss in vancomycin binding affinity for D-Ala-D-Lac into lost H-bond and repulsive lone pair contributions. Abstract Text:

Casey C McComas,Brendan M Crowley,Dale L Boger,

The binding affinity of 4, which incorporates a methylene (CH2) in place of the key linking amide of Ac2-l-Lys-d-Ala-d-Ala, for vancomycin was compared with that of Ac2-l-Lys-d-Ala-d-Ala (3) and Ac2-l-Lys-d-Ala-d-Lac (5). The vancomycin affinity for 4 was approximately 10-fold less than that of 3, but 100-fold greater than that of 5. This suggests that the reduced binding affinity of 5 (4.1 kcal/mol) may be attributed to both the loss of a key H-bond (1.5 kcal/mol) and a destabilizing lone pair/lone pair electrostatic interaction introduced with the ester oxygen of 5 (2.6 kcal/mol) with the latter, not the H-bond, being responsible for the largest share of the 1000-fold reduction.

Partitioning the loss in vancomycin binding affinity for D-Ala-D-Lac into lost H-bond and repulsive lone pair contributions. Publishing Authors By Initials

CC McComas,BM Crowley,DL Boger,

For similar carbohydrates: glycoconjugates: glycopeptides: vancomycin research abstracts see: carbohydrates: glycoconjugates: glycopeptides: vancomycin research

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Partitioning the loss in vancomycin binding affinity for D-Ala-D-Lac into lost H-bond and repulsive lone pair contributions. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of the American Chemical Society

VOLUME: 125

Page Numbers: 9314-5

Journal Abbreviation: J. Am. Chem. Soc.

ISSN: 0002-7863

DAY: 6

MONTH: Aug

YEAR: 2003

Partitioning the loss in vancomycin binding affinity for D-Ala-D-Lac into lost H-bond and repulsive lone pair contributions. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7503056

Partitioning the loss in vancomycin binding affinity for D-Ala-D-Lac into lost H-bond and repulsive lone pair contributions. Keywords Mesh Terms:

KEYWORDS: Vancomycin

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Partitioning the loss in vancomycin binding affinity for D-Ala-D-Lac into lost H-bond and repulsive lone pair contributions. Information

Substance Name: N(alpha), N-(epsilon)-diacetyl-lysyl-ala

Registry Number: 24570-39-6

Grant and Affiliation Information for Partitioning the loss in vancomycin binding affinity for D-Ala-D-Lac into lost H-bond and repulsive lone pair contributions.

AFFILIATION: Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA 41101

ACRONYM: CA

MEDLINETA: J Am Chem Soc

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