Structural modification and antitumor activity of antimicrobial peptide HYL  

作　　者：Minghao Wu Qing Chen Yingdi Wang Yulei Li Xia Zhao Qi Chang 

机构地区：[1]Key Laboratory of Marine Drugs,Ministry of Education,School of Medicine and Pharmacy,Ocean University of China,Qingdao 266003,China [2]Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology,Qingdao 266237,China

出　　处：《Chinese Chemical Letters》2020年第5期1288-1292,共5页中国化学快报（英文版）

基　　金：supported by NSFC-Shandong Joint Fund(No.U1606403);Innovation Project of Qingdao National Laboratory for Marine Science and Technology(No.2015ASKJ02)。

摘　　要：HYL derived from the venom of the solitary bee Hylaeus signatus(Hymenoptera:Colletidae)is anα-helical antimicrobial peptide with 16 residues.To explore whether HYL can be applied in anti-tumor therapy,we synthesized HYL and further modified its structure by using a solid-phase synthesis method,and then evaluated their antitumor activities.Firstly,we identified the key residues of HYL by alanine scanning strategy,and then a series of stapled peptides were synthesized by hydrocarbon stapling strategy without destroying the key residues.All the stapled peptides of HYL showed significant improvement not only inα-helicity,but also in antitumor activity and protease resistance when compared to the parent peptide HYL.The results showed that hydrophobicity and amphiphilicity are important factors affecting the antitumor activity of HYL,and the stapling strategy can significantly affect the proteolytic stability and helicity of HYL.What’s more,we find that the stapled peptides HYL-14,HYL-16 and HYL-18 show a promising prospect for novel anti-tumor drug development.

关 键 词：HYL α-Helical peptide Stapled peptide Hydrocarbon stapling strategy Antitumor activity Solid-phase synthesis 

分 类 号：TQ464.7[化学工程—制药化工]