Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/106474
Title: Structure-Based Design, Synthesis and Bioactivity of a New Anti-TNFα Cyclopeptide
Authors: Idress, Mohannad
Milne, Bruce F. 
Thompson, Gary S.
Trembleau, Laurent
Jaspars, Marcel 
Houssen, Wael E.
Keywords: cyclic peptides; NMR structure; drug design; protein–protein interaction
Issue Date: 19-Feb-2020
Publisher: MDPI
metadata.degois.publication.title: Molecules
metadata.degois.publication.volume: 25
metadata.degois.publication.issue: 4
Abstract: As opposed to small molecules, macrocyclic peptides possess a large surface area and are recognised as promising candidates to selectively treat diseases by disrupting specific protein-protein interactions (PPIs). Due to the difficulty in predicting cyclopeptide conformations in solution, the de novo design of bioactive cyclopeptides remains significantly challenging. In this study, we used the combination of conformational analyses and molecular docking studies to design a new cyclopeptide inhibitor of the interaction between the human tumour necrosis factor alpha (TNFα) and its receptor TNFR-1. This interaction is a key in mediating the inflammatory response to tissue injury and infection in humans, and it is also an important causative factor of rheumatoid arthritis, psoriasis and inflammatory bowel disease. The solution state NMR structure of the cyclopeptide was determined, which helped to deduce its mode of interaction with TNFα. TNFα sensor cells were used to evaluate the biological activity of the peptide.
URI: https://hdl.handle.net/10316/106474
ISSN: 1420-3049
DOI: 10.3390/molecules25040922
Rights: openAccess
Appears in Collections:I&D CFis - Artigos em Revistas Internacionais

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