Optimization and bioevaluation of Cdc37-derived peptides: An insight into Hsp90-Cdc37 protein-protein interaction modulators
Optimization and bioevaluation of Cdc37-derived peptides: An insight into Hsp90-Cdc37 protein-protein interaction modulators
复制标题
Cdc37 衍生肽的优化和生物评价：深入了解 Hsp90-Cdc37 蛋白质-蛋白质相互作用调节剂。
DOI：
10.1016/j.bmc.2016.10.028
复制
发表时间：
2017
影响因子：
3.5
通讯作者：
Xu Xiao Li
中科院分区：
文献类型：
--
作者：
Wang Lei;Li Li;Fu Wei Tao;Jiang Zheng Yu;You Qi Dong;Xu Xiao Li
Targeting Hsp90-Cdc37 protein-protein interaction (PPI) is becoming an alternative approach for future anti-cancer drug development. We previously reported the discovery of an eleven-residue peptide (Pep-1) with micromolar activity for the disruption of Hsp90-Cdc37 PPI. Efforts to improve upon thePep-1led to the discovery of more potent modulators for Hsp90-Cdc37 PPI. Through the analysis of peptides binding patterns, more peptides were designed for further verification which resulted inPep-5, the shortest peptide targeting Hsp90-Cdc37, exerting the optimal structure and the most efficient binding mode. Subsequent MD simulation analysis also confirmed thatPep-5could perform more stable binding ability and better ligand properties thanPep-1. Under the premise of retentive binding capacity,Pep-5exhibited lower molecular weight and higher ligand efficiency with a Kdvalue of 5.99 μM (Pep-1Kd= 6.90 μM) in both direct binding determination and biological evaluation. The optimal and shortestPep-5might provide a breakthrough and a better model for the future design of small molecule inhibitors targeting Hsp90-Cdc37 PPI.
