Engineering pro-angiogenic peptides using stable, disulfide-rich cyclic scaffolds

Chan, Lai Y., Gunasekera, Sunithi, Henriques, Sonia T., Worth, Nathalie F., Le, Sarah-Jane, Clark, Richard J., Campbell, Julie H., Craik, David J., and Daly, Norelle L. (2011) Engineering pro-angiogenic peptides using stable, disulfide-rich cyclic scaffolds. Blood, 118 (25). pp. 6709-6717.

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Fragments from the extracellular matrix proteins laminin and osteopontin and a sequence from VEGF have potent proangiogenic activity despite their small size (< 10 residues). However, these linear peptides have limited potential as drug candidates for therapeutic angiogenesis because of their poor stability. In the present study, we show that the therapeutic potential of these peptides can be significantly improved by "grafting" them into cyclic peptide scaffolds. Momordica cochinchinensis trypsin inhibitor-II (MCoTI-II) and sunflower trypsin inhibitor-1 (SFTI-1), naturally occurring, plant-derived cyclic peptides of 34 and 14 residues, respectively, were used as scaffolds in this study. Using this approach, we have designed a peptide that, in contrast to the small peptide fragments, is stable in human serum and at nanomolar concentration induces angiogenesis in vivo. This is the first report of using these scaffolds to improve the activity and stability of angiogenic peptide sequences and is a promising approach for promoting angiogenesis for therapeutic uses.

Item ID: 27007
Item Type: Article (Research - C1)
ISSN: 1528-0020
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: 401600
Date Deposited: 24 May 2013 02:37
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1101 Medical Biochemistry and Metabolomics > 110106 Medical Biochemistry: Proteins and Peptides (incl Medical Proteomics) @ 100%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 100%
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