Chorev M, Goodman M
Department of Pharmaceutical Chemistry, Faculty of Medicine, Hebrew University, Jerusalem, Israel.
Trends Biotechnol. 1995 Oct;13(10):438-45. doi: 10.1016/S0167-7799(00)88999-4.
Main-chain peptidomimetics based on peptide-bond reversal and inversion of chirality represent important structural alterations for peptides and proteins, and are highly significant for biotechnology; these modifications have been widely applied: the D-HIV-protease dimer cleaves only all-D substrate; an all-D-hexapeptide opioid is able to produce analgesia following intraperitoneal administration. Antigenicity and immunogenicity can be achieved by metabolically stable antigens such as all-D- and retro-inverso-isomers of natural antigenic peptides. Isomers, including the retro- and retro-inverso- forms, of hybrid peptides derived from cercropin A and melittin, maintain antimicrobial activity. Therefore, an insight is provided into structure-activity relationships and the rational design of biologically important isomeric peptides.
基于肽键反转和手性翻转的主链肽模拟物代表了肽和蛋白质重要的结构改变，对生物技术具有高度重要性；这些修饰已得到广泛应用：D型HIV蛋白酶二聚体仅切割全D型底物；全D型六肽阿片样物质腹腔注射后能够产生镇痛作用。代谢稳定的抗原（如天然抗原肽的全D型和反转异构体）可实现抗原性和免疫原性。源自杀菌肽A和蜂毒肽的杂合肽的异构体，包括反转和反向反转形式，保持抗菌活性。因此，深入了解了结构-活性关系以及生物学上重要的异构肽的合理设计。
