D-Ala-D-Lac binding is not required for the high activity of vancomycin dimers against vancomycin resistant enterococci
D-Ala-D-Lac binding is not required for the high activity of vancomycin dimers against vancomycin resistant enterococci
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DOI：
10.1021/ja0359761
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发表时间：
2003-07-23
影响因子：
15
通讯作者：
Ellman, JA
中科院分区：
文献类型：
--
作者：
Jain, RK;Trias, J;Ellman, JA
万古霉素的共价二聚和寡聚是开发抗万古霉素耐药肠球菌 (VRE) 活性类似物的重要且广泛使用的策略。在这里，我们进行了研究，以探讨肽结合 (Lys-d-Ala-d-Lac) 在共价连接的万古霉素二聚体的高抗 VRE 活性中的作用。制备了受损万古霉素（去亮氨酰）的共价二聚体，并测量了它们的抗 VRE 活性和对各种模型肽的结合亲和力。尽管与相应的完整万古霉素二聚体相比，对几种模型肽的亲和力显着降低，但这些受损的二聚体仍保持良好的抗 VRE 活性。这些结果强烈表明，共价万古霉素二聚体的高抗 VRE 活性是由 Lys-d-Ala-d-Lac 结合以外的机制赋予的。
Covalent dimerization and oligomerization of vancomycin is an important and extensively used strategy to develop analogues active against vancomycin resistant enteroccoci (VRE). Here, we have carried out investigations to probe the role of peptide binding (Lys-d-Ala-d-Lac) in the high anti-VRE activities of covalently linked vancomycin dimers. Covalent dimers of damaged vancomycin (desleucyl) were prepared, and their anti-VRE activities and binding affinities toward various model peptides were measured. Despite the dramatic loss in affinity toward several model peptides in comparison to the corresponding intact vancomycin dimers, these damaged dimers maintained good activity against VRE. These results strongly suggest that the high anti-VRE activities of covalent vancomycin dimers are conferred from mechanisms other than Lys-d-Ala-d-Lac binding.