Engineering of an anti-inflammatory peptide based on the disulfide-rich linaclotide scaffold
Cobos, Claudia, Bansal, Paramjit S., Jones, Linda, Wangchuk, Phurpa, Wilson, David, Loukas, Alex, and Daly, Norelle L. (2018) Engineering of an anti-inflammatory peptide based on the disulfide-rich linaclotide scaffold. Biomedicines, 6 (4). 97.
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Abstract
Inflammatory bowel diseases are a set of complex and debilitating diseases, for which there is no satisfactory treatment. Peptides as small as three amino acids have been shown to have anti-inflammatory activity in mouse models of colitis, but they are likely to be unstable, limiting their development as drug leads. Here, we have grafted a tripeptide from the annexin A1 protein into linaclotide, a 14-amino-acid peptide with three disulfide bonds, which is currently in clinical use for patients with chronic constipation or irritable bowel syndrome. This engineered disulfide-rich peptide maintained the overall fold of the original synthetic guanylate cyclase C agonist peptide, and reduced inflammation in a mouse model of acute colitis. This is the first study to show that this disulfide-rich peptide can be used as a scaffold to confer a new bioactivity.
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