5VAV
Design of a novel cyclic peptide that alleviates symptoms in a murine model of inflammatory bowel disease
Summary for 5VAV
| Entry DOI | 10.2210/pdb5vav/pdb |
| Related | 5VFW |
| NMR Information | BMRB: 30274 |
| Descriptor | cyc-MC12 (1 entity in total) |
| Functional Keywords | inflammatory bowel disease, de novo protein |
| Biological source | Helianthus annuus |
| Total number of polymer chains | 1 |
| Total formula weight | 1591.83 |
| Authors | Daly, N.L.,Cobos Caceres, C. (deposition date: 2017-03-28, release date: 2017-05-10, Last modification date: 2024-10-16) |
| Primary citation | Cobos Caceres, C.,Bansal, P.S.,Navarro, S.,Wilson, D.,Don, L.,Giacomin, P.,Loukas, A.,Daly, N.L. An engineered cyclic peptide alleviates symptoms of inflammation in a murine model of inflammatory bowel disease. J. Biol. Chem., 292:10288-10294, 2017 Cited by PubMed 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. PubMed: 28473469DOI: 10.1074/jbc.M117.779215 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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