典型文献
Bicyclic stapled peptides based on p53 as dual inhibitors for the interactions of p53 with MDM2 and MDMX
文献摘要：
In recent years,the strategy of inhibiting the interactions of p53 with murine double minute 2(MDM2)and murine double minute X(MDMX)has been proved to be a promising approach for tumor therapy.However,the poor proteolytical stability and low intracellular delivery efficiency of peptide inhibitors limit their clinical application.Here,we designed and synthesized the bicyclic stapled peptides based on p53 by combining all-hydrocarbon stapling and lactam stapling strategies.We demonstrated that bi-cyclic stapled peptide p53-16 significantly improved α-helicity and proteolytic stability.Especially,p53-16 showed nanomolar binding affinity for MDM2 and MDMX.In addition,p53-16 could penetrate the cell membrane,and selectively inhibited the activity of tumor cells via activating p53 pathway in vitro.Our data suggest that p53-16 is a potential dual inhibitor of MDM2 and MDMX interactions.The bicyclic sta-pling strategy is a promising drug design strategy for protein-protein interactions inhibitors.
文献关键词：
中图分类号：
作者姓名：
Hongjin Li;Xiangyan Chen;Minghao Wu;Panpan Song;Xia Zhao
作者机构：
Key Laboratory of Marine Drugs,Ministry of Education,School of Medicine and Pharmacy,Ocean University of China,Qingdao 266003,China;Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology,Qingdao 266237,China
文献出处：
引用格式：
[1]Hongjin Li;Xiangyan Chen;Minghao Wu;Panpan Song;Xia Zhao-.Bicyclic stapled peptides based on p53 as dual inhibitors for the interactions of p53 with MDM2 and MDMX)[J].中国化学快报（英文版）,2022(03):1254-1258
A类：
Bicyclic,stapled,MDMX,proteolytical,stapling
B类：
peptides,p53,dual,inhibitors,interactions,MDM2,In,recent,years,strategy,inhibiting,murine,double,minute,has,been,promising,approach,tumor,therapy,However,poor,stability,low,intracellular,delivery,efficiency,limit,their,clinical,application,Here,designed,synthesized,bicyclic,by,combining,hydrocarbon,lactam,strategies,We,demonstrated,that,significantly,improved,helicity,Especially,showed,nanomolar,binding,affinity,addition,could,penetrate,membrane,selectively,inhibited,activity,cells,via,activating,pathway,vitro,Our,data,suggest,potential,drug,protein
AB值：
0.445718
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