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

doi:10.3390/molecules171112533

This article is

freely available
re-usable

Molecules 2012, 17(11), 12533-12552; doi:10.3390/molecules171112533

Review

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

Michael Reinwarth^†, Daichi Nasu^†, Harald Kolmar and Olga Avrutina*

Institute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Petersenstraße 22, D-64287 Darmstadt, Germany ^† These authors contributed equally to this work.

* Author to whom correspondence should be addressed.

Received: 15 August 2012; in revised form: 19 September 2012 / Accepted: 22 October 2012 / Published: 24 October 2012

(This article belongs to the Special Issue Chemical Protein and Peptide Synthesis)

Download PDF Full-Text [496 KB, uploaded 24 October 2012 14:59 CEST]

Abstract: 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.

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

Article Statistics

Click here to load and display the download statistics.

Cite This Article

MDPI and ACS Style

Reinwarth, M.; Nasu, D.; Kolmar, H.; Avrutina, O. Chemical Synthesis, Backbone Cyclization and Oxidative Folding of Cystine-knot Peptides — Promising Scaffolds for Applications in Drug Design. Molecules 2012, 17, 12533-12552.

AMA Style

Reinwarth M, Nasu D, Kolmar H, Avrutina O. Chemical Synthesis, Backbone Cyclization and Oxidative Folding of Cystine-knot Peptides — Promising Scaffolds for Applications in Drug Design. Molecules. 2012; 17(11):12533-12552.

Chicago/Turabian Style

Reinwarth, Michael; Nasu, Daichi; Kolmar, Harald; Avrutina, Olga. 2012. "Chemical Synthesis, Backbone Cyclization and Oxidative Folding of Cystine-knot Peptides — Promising Scaffolds for Applications in Drug Design." Molecules 17, no. 11: 12533-12552.

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert