Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089-9121, U.S.A.
Department of Chemistry, University of Southern California, Los Angeles, CA 90089-9121, U.S.A.
Biochem J. 2019 Jan 11;476(1):67-83. doi: 10.1042/BCJ20180792.
The use of disulfide-rich backbone-cyclized polypeptides, as molecular scaffolds to design a new generation of bioimaging tools and drugs that are potent and specific, and thus might have fewer side effects than traditional small-molecule drugs, is gaining increasing interest among the scientific and in the pharmaceutical industries. Highly constrained macrocyclic polypeptides are exceptionally more stable to chemical, thermal and biological degradation and show better biological activity when compared with their linear counterparts. Many of these relatively new scaffolds have been also found to be highly tolerant to sequence variability, aside from the conserved residues forming the disulfide bonds, able to cross cellular membranes and modulate intracellular protein-protein interactions both and These properties make them ideal tools for many biotechnological applications. The present study provides an overview of the new developments on the use of several disulfide-rich backbone-cyclized polypeptides, including cyclotides, θ-defensins and sunflower trypsin inhibitor peptides, in the development of novel bioimaging reagents and therapeutic leads.
利用富含二硫键的骨架环化多肽作为分子支架，设计新一代的生物成像工具和药物，这些工具和药物具有高效和特异性，因此可能比传统的小分子药物副作用更小，这在科学界和制药行业中引起了越来越多的兴趣。高度约束的大环多肽在化学、热和生物降解方面异常稳定，并且与线性对应物相比，表现出更好的生物活性。除了形成二硫键的保守残基外，这些相对较新的支架中的许多还被发现对序列变异性具有高度耐受性，能够穿过细胞膜并调节细胞内蛋白质-蛋白质相互作用。这些特性使它们成为许多生物技术应用的理想工具。本研究概述了几种富含二硫键的骨架环化多肽（包括环肽、θ-防御素和向日葵胰蛋白酶抑制剂肽）在新型生物成像试剂和治疗先导物开发中的新进展。
