Lee Jung-Goo, Sagui Celeste, Roland Christopher
Center for High Performance Simulations (CHiPS) and Department of Physics, North Carolina State University, Raleigh, NC 27695-8202, USA.
J Phys Chem B. 2005 Nov 3;109(43):20588-96. doi: 10.1021/jp0548117.
The recent rise of vancomycin-resistant enterococci (VRE) and vancomycin-resistant Staphylococcus aureus (VRSA) has given new impetus to the study of the binding between glycopeptide antibiotics and bacterial cell wall termini. Here, we report on an extensive first principles investigation of the binding of vancomycin, avoparcin, teicoplanin, and ristocetin aglycons with dipetides, Ac-d-Ala-X, where X = d-Lac and d-Ser (characteristic of VREs) and X = d-Ala, Gly (characteristic of non-VREs), and a model "methylated d-Ala" CH(2)CH(CH(3))COO(-), in liquid as well as gas phase. The gas-phase ordering of the binding, from strongest to weakest, is Gly, d-Ala, d-Ser, CH(2)CH(CH(3))COO(-), and d-Lac. Calculations show that the order of the Gly and d-Ala binding is reversed in solution. The results are in good agreement with recent experimental findings.
耐万古霉素肠球菌（VRE）和耐万古霉素金黄色葡萄球菌（VRSA）的近期出现，为糖肽类抗生素与细菌细胞壁末端结合的研究注入了新的动力。在此，我们报告了对万古霉素、阿伏帕星、替考拉宁和瑞斯托菌素苷元与二肽Ac-d-Ala-X结合的广泛第一性原理研究，其中X = d-Lac和d-Ser（VRE的特征）以及X = d-Ala、Gly（非VRE的特征），还有一个模型“甲基化d-Ala”CH(2)CH(CH(3))COO(-)，研究在液相和气相中进行。结合的气相排序，从最强到最弱，依次为Gly、d-Ala、d-Ser、CH(2)CH(CH(3))COO(-)和d-Lac。计算表明，在溶液中Gly和d-Ala的结合顺序相反。结果与最近的实验发现高度吻合。
