5VAV

Design of a novel cyclic peptide that alleviates symptoms in a murine model of inflammatory bowel disease

5VAV の概要

• エントリーDOI: 10.2210/pdb5vav/pdb
• 関連するPDBエントリー: 5VFW
• NMR情報: BMRB: 30274
• 分子名称: cyc-MC12 (1 entity in total)
• 機能のキーワード: inflammatory bowel disease, de novo protein
• 由来する生物種: Helianthus annuus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1591.83

構造登録者

Daly, N.L.,Cobos Caceres, C. (登録日: 2017-03-28, 公開日: 2017-05-10, 最終更新日: 2024-10-16)

主引用文献

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

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: 28473469
DOI: 10.1074/jbc.M117.779215

実験手法

SOLUTION NMR