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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.

Original publication

DOI

10.3390/molecules191221529

Type

Journal article

Journal

Molecules (Basel, Switzerland)

Publication Date

01/2014

Volume

19

Pages

21529 - 21540

Addresses

Proxima Concepts Limited, c/o London Bioscience Innovation Centre, 2 Royal College Street, London NW1 0NH, UK. rogernew@proximaconcepts.com.

Keywords

Cell Line, Macrophages, Animals, Mice, Peptides, Cyclic, Lipopolysaccharides, Tumor Necrosis Factor-alpha, Interleukin-6, Immunologic Factors, Down-Regulation, Drug Design, Micelles