摘要
Modulation of protein fate decision and protein homeostasis plays a significant role in altering the protein level,which acts as an orientation to develop drugs with new mechanisms.The molecular chaperones exert significant biological functions on modulation of protein fate decision and protein homeostasis under constantly changing environmental conditions through extensive protein-protein interactions(PPIs)with their client proteins.With the help of molecular chaperone machinery the processes of protein folding,trafficking,quality control and degradation of client proteins could be arranged properly.The core members of molecular chaperones,including heat shock proteins(HSPs)family and their co-chaperones,are emerging as potential drug targets since they are involved in numerous disease conditions.Development of small molecule modulators targeting not only chaperones themselves but also the PPIs among chaperones,co-chaperones and clients is attracting more and more attention.These modulators are widely used as chemical tools to study chaperone networks as well as potential drug candidates for a broader set of diseases.Here,we reviewed the key checkpoints of molecular chaperone machinery HSPs as well as their co-chaperones to discuss the small molecules targeting on them for modulation of protein fate decision.
基金
the financial support by National Natural Science Foundation of China(81773639,81773581,81872737 and 81930100)
the Natural Science Foundation of Jiangsu Province(BK20190559,BK20160746 China)
National Science&Technology Major Project‘Key New Drug Creation and Manufacturing Program’(Nos.2018ZX09711002 and 2017ZX09302003,China)
the Priority Academic Program Development of Jiangsu Higher Education Institutions
the Fundamental Research Funds for the Central Universities of China Pharmaceutical University(2632018ZD15,China)
the Double First Class Innovation Team of China Pharmaceutical University(CPU2018GY02,China)
Program for Outstanding Scientific and Technological Innovation Team of Jiangsu Higher Education
the Young Elite Scientists Sponsorship Program by CAST
the Jiangsu Qing Lan Project