Cyclotides, a Novel Ultrastable Polypeptide Scaffold for Drug Discovery

Author(s): Andrew Gould, Yanbin Ji, Teshome L. Aboye, Julio A. Camarero.

Journal Name: Current Pharmaceutical Design

Volume 17 , Issue 38 , 2011


Cyclotides are a unique and growing family of backbone cyclized peptides that also contain a cystine knot motif built from six conserved cysteine residues. This unique circular backbone topology and knotted arrangement of three disulfide bonds makes them exceptionally stable to thermal, chemical, and enzymatic degradation compared to other peptides of similar size. Aside from the conserved residues forming the cystine knot, cyclotides have been shown to have high variability in their sequences. Consisting of over 160 known members, cyclotides have many biological activities, ranging from anti-HIV, antimicrobial, hemolytic, and uterotonic capabilities; additionally, some cyclotides have been shown to have cell penetrating properties. Originally discovered and isolated from plants, cyclotides can also be produced synthetically and recombinantly. The high sequence variability, stability, and cell penetrating properties of cyclotides make them potential scaffolds to be used to graft known active peptides or engineer peptide-based drug design. The present review reports recent findings in the biological diversity and therapeutic potential of natural and engineered cyclotides.

Keywords: Cyclotides, cyclic peptides, peptide therapeutics, drug discovery, drug design, cysteine residues, enzymatic degradation, anti-HIV, cystine-knot scaffold, neurotensin antagonism

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Article Details

Year: 2011
Page: [4294 - 4307]
Pages: 14
DOI: 10.2174/138161211798999438
Price: $58

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