Binding of a dimeric derivative of vancomycin to L-Lys-D-Ala-D-lactate in solution and at a surface.
Binding of a dimeric derivative of vancomycin to L-Lys-D-Ala-D-lactate in solution and at a surface.
复制标题
万古霉素二聚体衍生物在溶液中和表面与 L-Lys-D-Ala-D-乳酸结合。
DOI：
10.1016/s1074-5521(99)80047-7
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Warren,HS
中科院分区：
文献类型：
--
作者：
Rao,J;Yan,L;Lahiri,J;Whitesides,GM;Weis,RM;Warren,HS
BackgroundThe emergence of bacteria that are resistant to vancomycin (V), a glycopeptide antibiotic, results from the replacement of the carboxy-terminal d-Ala-d-Ala of bacterial cell wall precursors by d-Ala-d-lactate. Recently, it has been demonstrated that covalent dimeric variants of V are active against vancomycin-resistant enterococci (VRE). To study the contribution of divalency to the activities of these variants, we modeled the interactions of V and a dimeric V with l-Lys-d-Ala-d-lactate, an analog of the cell-wall precursors of the vancomycin-resistant bacteria.ResultsA dimeric derivative of V (V-Rd-V) was found to be much more effective than V in inhibiting the growth of VRE. The interactions of V and V-Rd-V with a monomeric lactate ligand — diacetyl-l-Lys-d-Ala-d-lactate (AccKdAdLac) — and a dimeric derivative of l-Lys-d-Ala-d-lactate (Lac-R′d-Lac) in solution have been examined using isothermal titration calorimetry and UV spectroscopy titrations; the results reveal that V-Rd-V binds Lac-R′d-Lac approximately 40 times more tightly than V binds Ac2KdAdLac. Binding of V and of V-Rd-V toNα-Ac-l-Lys-d-Ala-d-lactate presented on the surface of mixed self-assembled monolayers (SAMs) of alkanethiolates on gold indicates that the apparent off-rate for dissociation of V-Rd-V from the surface is much slower than that of V from the same surface.ConclusionsThe results are compatible with the hypothesis that divalency is responsible for tight binding, which correlates with small values of minimum inhibitory concentrations of V and V-Rd-V.
