Journal of the American Chemical Society 2003-08-06

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

Casey C McComas, Brendan M Crowley, Dale L Boger

Index: J. Am. Chem. Soc. 125(31) , 9314-5, (2003)

Full Text: HTML

Abstract

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.

Related Compounds

  • Ac-Lys(Ac)-D-Ala...

Related Articles:

Conformational studies of resin-bound vancomycin and the complex of vancomycin and Ac2-L-Lys-D-Ala-D-Ala.

2005-01-01

[J. Comb. Chem. 7(1) , 123-9, (2005)]

Isolation of the membrane-bound 26 000-Mr penicillin-binding protein of Streptomyces strain K15 in the form of a penicillin-sensitive D-alanyl-D-alanine-cleaving transpeptidase.

1982-10-01

[Biochem. J. 207 , 109, (1982)]

Conformational analysis of peptide substrates and inhibitors of the Zn2+ G and serine R61 D-alanyl-D-alanine peptidases.

1981-12-01

[Eur. J. Biochem. 121(1) , 221-32, (1981)]

Preparation of biologically active ristocetin derivatives: replacements of the 1'-amino group.

1985-09-01

[J. Med. Chem. 28(9) , 1371-5, (1985)]

Dual nano-electrospray for probing solution interactions and fast reactions of complex biomolecules.

2012-01-01

[Eur. J. Mass Spectrom. (Chichester, Eng.) 18(5) , 439-46, (2012)]

More Articles...