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.

Item ID: 56843
Item Type: Article (Research - C1)
ISSN: 2227-9059
Keywords: anti-inflammatory, peptides and TNBS
Copyright Information: © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Date Deposited: 16 Jan 2019 01:07
FoR Codes: 03 CHEMICAL SCIENCES > 0304 Medicinal and Biomolecular Chemistry > 030401 Biologically Active Molecules @ 80%
11 MEDICAL AND HEALTH SCIENCES > 1101 Medical Biochemistry and Metabolomics > 110104 Medical Biochemistry: Lipids @ 20%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970103 Expanding Knowledge in the Chemical Sciences @ 60%
97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 30%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 10%
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