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

Molecules

Roger New²  Gurpal S. Bansal²  Malgorzata Dryjska²  Michal Bogus²  Patricia Green¹  Marc Feldmann¹  Fionula Brennan¹ 

[1] Kennedy Institute of Rheumatology, Roosevelt Drive, University of Oxford, Headington OX3 7FY, UK; E-Mails:;Proxima Concepts Limited, c/o London Bioscience Innovation Centre, 2 Royal College Street, London NW1 0NH, UK; E-Mails:

关键词: cyclic peptide;    TNF;    interleukin 6;    rheumatoid arthritis;    lipo amino acid;   

DOI  :  10.3390/molecules191221529

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.