不需要D-Ala-D-lac结合,因为万科米辛二次体对抗抗万科米辛耐药性肠球菌的高活性
Rishi K Jain1, Joaquim Trias, Jonathan A Ellman
1Department of Chemistry, University of California, Berkeley, California 94720, USA.
Journal of the American Chemical Society
|July 17, 2003
概括
共价范胺二聚体对抗抗范胺耐药性肠球菌 (VRE) 具有高活性. 它们的有效性来自于超出与Lys-d-Ala-d-Lac结合的机制,即使损坏了.
科学领域:
- 药用化学 医学化学
- 微生物学 微生物学
- 药物发现 药物发现 药物发现
背景情况:
- 肠球菌 (VRE) 中的万科米辛耐药性是一个重大的临床挑战.
- 范科米的共价二聚化是开发新型抗VRE药物的关键策略.
研究的目的:
- 为了研究结对抗VRE活性中的胺结合的作用.
- 为了确定作用机制是否依赖于与Lys-d-Ala-d-Lac.Lac.结合.
主要方法:
- 从受损的万科米辛 (desleucyl) 中制备共价二次体.
- 测量这些二次体的抗VRE活性.
- 对模型 (Lys-d-Ala-d-Lac) 的结合 afinities 的评估.
主要成果:
- 与完整的二分体相比,受损的万科米辛二分体对模型的结合亲和力较低.
- 尽管结合减少了,但受损的二分体仍然保持了显著的抗VRE活性.
- 这表明一种独立于结合的机制有助于它们的有效性.
结论:
- 共价万科米辛二聚体的高抗VRE活性不仅仅取决于与Lys-d-Ala-d-Lac点的结合.
- 替代机制对这些万科米辛类似物对VRE的疗效有着显著的贡献.
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