An engineered cyclic peptide alleviates symptoms of inflammation in a murine model of inflammatory bowel disease

Cobos Caceres, Claudia, Bansal, Paramjit S., Navarro, Severine, Wilson, David, Don, Laurianne, Giacomin, Paul, Loukas, Alex, and Daly, Norelle L. (2017) An engineered cyclic peptide alleviates symptoms of inflammation in a murine model of inflammatory bowel disease. Journal of Biological Chemistry, 292 (24). pp. 10288-10294.

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Abstract

Inflammatory bowel diseases (IBDs) are a set of complex and debilitating diseases for which there is no satisfactory treatment. Recent studies have shown that small peptides show promise for reducing inflammation in models of IBD. However, these small peptides are likely to be unstable and rapidly cleared from the circulation, and therefore, if not modified for better stability, represent non-viable drug leads. We hypothesized that improving the stability of these peptides by grafting them into a stable cyclic peptide scaffold may enhance their therapeutic potential. Using this approach, we have designed a novel cyclic peptide that comprises a small bioactive peptide from the annexin A1 protein grafted into a sunflower trypsin inhibitor cyclic scaffold. We used native chemical ligation to synthesize the grafted cyclic peptide. This engineered cyclic peptide maintained the overall fold of the naturally occurring cyclic peptide, was more effective at reducing inflammation in a mouse model of acute colitis than the bioactive peptide alone, and showed enhanced stability in human serum. Our findings suggest that the use of cyclic peptides as structural backbones offers a promising approach for the treatment of IBD and potentially other chronic inflammatory conditions.

Item ID: 50180
Item Type: Article (Research - C1)
ISSN: 1083-351X
Funders: National Health and Medical Research Council of Australia (NHMRC), Australian Research Council (ARC)
Projects and Grants: NHMRC 1020114, ARC FF110100226
Date Deposited: 13 Sep 2017 02:49
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 > 970106 Expanding Knowledge in the Biological Sciences @ 100%
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