镜像配基筛选:克服“酶屏障”的多肽、寡核苷酸药物研发技术  

Mirror-image isomers screening:Overcoming the enzyme barriers for the development of peptide and oligonucleotide therapeutics

作　　者：李翀[1] 沈洁[2] 陆伟跃[2] 陆五元 

机构地区：[1]西南大学药学院,重庆400715 [2]复旦大学药学院,上海201203 [3]School of Medicine,University of Maryland

出　　处：《中国科学：化学》2011年第7期1112-1120,共9页SCIENTIA SINICA Chimica

基　　金：国家重点基础研究发展计划(973计划)(2007CB935800和2010CB934000);西南大学博士基金(SWU110028);西南大学基本科研业务费专项资金项目(XDJK2009C077)资助

摘　　要：生物体内存在的"酶屏障"是功能性多肽和寡核苷酸成药的重要瓶颈.以镜像噬菌体展示技术(mirror-image phage display)和镜像适配体筛选技术(Spiegelmer technology)为代表的镜像配基筛选技术能有效地克服这一屏障,获得对靶点具有特异识别能力且在生理条件下高度稳定的D型多肽和L型寡核苷酸配基,有望成为多肽或寡核苷酸类特异性药物研发的有利工具.本文主要综述镜像配基筛选技术的原理及其在药学领域的研究进展.The enzyme barriers in vivo greatly limited the development of peptide and oligonucleotide therapeutics.The mirror-image isomers screening including mirror-image phage display and Spiegelmer technology can obtain biostable D-peptides and L-oligonuclotides with high specificity to their targets,thus will be a promising technology for the development of novel peptide and oligonucleotide drugs.This review will focus on the principle of mirror-image isomers screening and highlight recent developments of this technology in the field of pharmaceutical research.

关 键 词：镜像噬菌体展示技术 镜像适配体筛选技术 D型多肽 L型寡核苷酸 

分 类 号：TQ464.7[化学工程—制药化工]