Engineering of an anti-inflammatory peptide based on the disulfide-rich linaclotide scaffold
Journal Publication ResearchOnline@JCUAbstract
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.
Journal
Biomedicines
Publication Name
N/A
Volume
6
ISBN/ISSN
2227-9059
Edition
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Issue
4
Pages Count
10
Location
N/A
Publisher
MDPI
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EISSN
N/A
DOI
10.3390/biomedicines6040097