Gould Andrew, Camarero Julio A
Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, 90089-9121, USA.
Department of Chemistry, University of Southern California, Los Angeles, CA, 90089-9121, USA.
Chembiochem. 2017 Jul 18;18(14):1350-1363. doi: 10.1002/cbic.201700153. Epub 2017 May 24.
Cyclotides are globular microproteins with a unique head-to-tail cyclized backbone, stabilized by three disulfide bonds forming a cystine knot. This unique circular backbone topology and knotted arrangement of three disulfide bonds makes them exceptionally stable to chemical, thermal, and biological degradation compared to other peptides of similar size. In addition, cyclotides have been shown to be highly tolerant to sequence variability, aside from the conserved residues forming the cystine knot. Cyclotides can also cross cellular membranes and are able to modulate intracellular protein-protein interactions, both in vitro and in vivo. All of these features make cyclotides highly promising as leads or frameworks for the design of peptide-based diagnostic and therapeutic tools. This article provides an overview on cyclotides and their applications as molecular imaging agents and peptide-based therapeutics.
环肽是一种球状微蛋白，具有独特的头尾环化主链，由三个二硫键稳定形成胱氨酸结。与其他类似大小的肽相比，这种独特的环状主链拓扑结构和三个二硫键的打结排列使其对化学、热和生物降解具有极高的稳定性。此外，除了形成胱氨酸结的保守残基外，环肽已被证明对序列变异性具有高度耐受性。环肽还可以穿过细胞膜，并能够在体外和体内调节细胞内蛋白质-蛋白质相互作用。所有这些特性使环肽作为基于肽的诊断和治疗工具的先导或框架极具前景。本文概述了环肽及其作为分子成像剂和基于肽的治疗剂的应用。
