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Molecules 2014, 19(12), 21529-21540; doi:10.3390/molecules191221529

Design and Optimisation of Bioactive Cyclic Peptides: Generation of a Down-Regulator of TNF Secretion

1
Proxima Concepts Limited, c/o London Bioscience Innovation Centre, 2 Royal College Street, London NW1 0NH, UK
2
Bone Medical Limited, 16 Ord Street, West Perth, WA 6005, Australia
3
Kennedy Institute of Rheumatology, Roosevelt Drive, University of Oxford, Headington OX3 7FY, UK
Deceased June 2012.
*
Author to whom correspondence should be addressed.
Received: 21 October 2014 / Revised: 9 December 2014 / Accepted: 10 December 2014 / Published: 22 December 2014
(This article belongs to the Section Medicinal Chemistry)
View Full-Text   |   Download PDF [906 KB, uploaded 22 December 2014]   |  

Abstract

Although strong binding interactions between protein receptor and ligand do not require the participation of a large number of amino acids in either site, short peptide chains are generally poor at recreating the types of protein-protein interactions which take place during cell recognition and signalling process, probably because their flexible backbones prevent the side chains from forming sufficiently rigid and stable epitopes, which can take part in binding with the desired strength and specificity. In a recently-reported study, it was shown that a proto-epitope containing F, R and S amino acids has the ability to down-regulate TNF secretion by macrophages. This paper extends these findings, putting those amino acids into a short cyclic peptide scaffold, and determining the optimal configuration required to overcome the problems of conformational instability, and give rise to molecules which have potential as therapeutic agents in human disease, such as rheumatoid arthritis. View Full-Text
Keywords: cyclic peptide; TNF; interleukin 6; rheumatoid arthritis; lipo amino acid cyclic peptide; TNF; interleukin 6; rheumatoid arthritis; lipo amino acid
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

New, R.; Bansal, G.S.; Dryjska, M.; Bogus, M.; Green, P.; Feldmann, M.; Brennan, F. Design and Optimisation of Bioactive Cyclic Peptides: Generation of a Down-Regulator of TNF Secretion. Molecules 2014, 19, 21529-21540.

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