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
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DOI：
10.1021/ja035901x
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发表时间：
2003-08-06
影响因子：
15
通讯作者：
Boger, DL
中科院分区：
文献类型：
--
作者：
McComas, CC;Crowley, BM;Boger, DL
用亚甲基(CH2)取代了关键连接酰胺Ac2-L-Lys-d-Ala-d-Ala，比较了其与Ac2-L-Lys-d-Ala-d-Ala(3)和Ac2-L-Lys-d-Ala-d-Lac(5)与万古霉素的亲和力。4对万古霉素的亲和力比3小约10倍，但比5大100倍。这表明，5的结合亲和力降低(4.1千卡/摩尔)可能是由于失去了关键的H键(1.5千卡/摩尔)，以及与5(2.6千卡/摩尔)的酯氧引入的不稳定的孤对/孤对静电相互作用，后者而不是H键，是1000倍还原的最大份额。
The binding affinity of4, 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 for4was approximately 10-fold less than that of3, but 100-fold greater than that of5. This suggests that the reduced binding affinity of5(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 of5(2.6 kcal/mol) with the latter, not the H-bond, being responsible for the largest share of the 1000-fold reduction.