Chemical Synthesis, Backbone Cyclization and Oxidative Folding of Cystine-knot Peptides — Promising Scaffolds for Applications in Drug Design

Molecules

Michael Reinwarth¹  Daichi Nasu¹  Harald Kolmar² 

[1] id="af1-molecules-17-12533">Institute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Petersenstraße 22, D-64287 Darmstadt, Germa

关键词: CCK;    cyclotide;    cystine knot;    ICK;    inhibitor;    knottin;    miniprotein;    native chemical ligation;    oxidative folding;   

DOI  :  10.3390/molecules171112533

来源: mdpi

【 摘 要 】

Cystine-knot peptides display exceptional structural, thermal, and biological stability. Their eponymous motif consists of six cysteine residues that form three disulfide bonds, resulting in a notably rigid structural core. Since they highly tolerate either rational or combinatorial changes in their primary structure, cystine knots are considered to be promising frameworks for the development of peptide-based pharmaceuticals. Despite their relatively small size (two to three dozens amino acid residues), the chemical synthesis route is challenging since it involves critical steps such as head-to-tail cyclization and oxidative folding towards the respective bioactive isomer. Herein we describe the topology of cystine-knot peptides, their synthetic availability and briefly discuss potential applications of engineered variants in diagnostics and therapy.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.