Cyclotides, a promising molecular scaffold for peptide‐based therapeutics

2010/01/01 by Krishnappa Jagadish, Julio A. Camarero · 23 citations
Biochemistry, Genetics and Molecular Biology · Agricultural and Biological Sciences · #Biochemical and Structural Characterization #Phytoplasmas and Hemiptera pathogens #Glycosylation and Glycoproteins Research

paper · pdf · doi:10.1002/bip.21433

Abstract

Abstract Cyclotides are a new emerging family of large plant‐derived backbone‐cyclized polypeptides (≈30 amino acids long) that share a disulfide‐stabilized core (three disulfide bonds) characterized by an unusual knotted structure. Their unique circular backbone topology and knotted arrangement of three disulfide bonds make them exceptionally stable to thermal, chemical, and enzymatic degradation compared to other peptides of similar size. Currently, more than 100 sequences of different cyclotides have been characterized, and the number is expected to increase dramatically in the coming years. Considering their stability and biological activities like anti‐HIV, uterotonic, and insecticidal, and also their abilities to cross the cell membrane, cyclotides can be exploited to develop new stable peptide‐based drugs. We have recently demonstrated the intriguing possibility of producing libraries of cyclotides inside living bacterial cells. This opens the possibility to generate large genetically encoded libraries of cyclotides that can then be screened inside the cell for selecting particular biological activities in a high‐throughput fashion. The present minireview reports the efforts carried out toward the selection of cyclotide‐based compounds with specific biological activities for drug design. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 94: 611–616, 2010. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at [email protected]

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