Head‐to‐Tail Cyclized Cystine‐Knot Peptides by a Combined Recombinant and Chemical Route of Synthesis

Abstract

Backbone cyclization of recombinantly produced cystine knot peptides, resulting in correctly folded macrocyclic disulfide-bridged peptides, is reported. It does not require protecting groups, takes place in aqueous solution, and is devoid of racemization and solubility problems. Scaling up to production of multimilligram amounts of iminocyclotides seems feasible. The resulting iminocyclotides are biologically active proteinase inhibitors—imino-cyclo-McoEeTIKKV was identified as the most potent proteinaceous inhibitor of human mast cell tryptase known. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2268/2008/z700452_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.