Structural highlights
FunctionANXA1_HUMAN Calcium/phospholipid-binding protein which promotes membrane fusion and is involved in exocytosis. This protein regulates phospholipase A2 activity. It seems to bind from two to four calcium ions with high affinity. Publication Abstract from PubMedInflammatory 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, which 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. An engineered cyclic peptide alleviates symptoms of inflammation in a murine model of inflammatory bowel disease.,Cobos Caceres C, Bansal PS, Navarro S, Wilson D, Don L, Giacomin P, Loukas A, Daly NL J Biol Chem. 2017 May 4. pii: jbc.M117.779215. doi: 10.1074/jbc.M117.779215. PMID:28473469[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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