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Chembiochem. 2013 Jan 2;14(1):137-46. doi: 10.1002/cbic.201200604. Epub 2012 Dec 11.

Oxidative folding of peptides with cystine-knot architectures: kinetic studies and optimization of folding conditions.

Author information

1
Institute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Petersenstr. 22, 64287 Darmstadt, Germany.

Abstract

Bioactive peptides often contain several disulfide bonds that provide the main contribution to conformational rigidity and structural, thermal, or biological stability. Among them, cystine-knot peptides-commonly named "knottins"-make up a subclass with several thousand natural members. Hence, they are considered promising frameworks for peptide-based pharmaceuticals. Although cystine-knot peptides are available through chemical and recombinant synthetic routes, oxidative folding to afford the bioactive isomers still remains a crucial step. We therefore investigated the oxidative folding of ten protease-inhibiting peptides from two knottin families, as well as that of an HIV entry inhibitor and of aprotinin, under two conventional sets of folding conditions and by a newly developed procedure. Kinetic studies identified folding conditions that resulted in correctly folded miniproteins with high rates of conversion even for highly hydrophobic and aggregation-prone peptides in concentrated solutions.

PMID:
23229141
DOI:
10.1002/cbic.201200604
[Indexed for MEDLINE]

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