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

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 sign...

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Detalles Bibliográficos
Autores principales: New, Roger, Bansal, Gurpal S., Dryjska, Malgorzata, Bogus, Michal, Green, Patricia, Feldmann, Marc, Brennan, Fionula
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271530/
https://www.ncbi.nlm.nih.gov/pubmed/25532847
http://dx.doi.org/10.3390/molecules191221529
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author New, Roger
Bansal, Gurpal S.
Dryjska, Malgorzata
Bogus, Michal
Green, Patricia
Feldmann, Marc
Brennan, Fionula
author_facet New, Roger
Bansal, Gurpal S.
Dryjska, Malgorzata
Bogus, Michal
Green, Patricia
Feldmann, Marc
Brennan, Fionula
author_sort New, Roger
collection PubMed
description 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.
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spelling pubmed-62715302018-12-28 Design and Optimisation of Bioactive Cyclic Peptides: Generation of a Down-Regulator of TNF Secretion New, Roger Bansal, Gurpal S. Dryjska, Malgorzata Bogus, Michal Green, Patricia Feldmann, Marc Brennan, Fionula Molecules Article 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. MDPI 2014-12-22 /pmc/articles/PMC6271530/ /pubmed/25532847 http://dx.doi.org/10.3390/molecules191221529 Text en © 2014 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 license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
New, Roger
Bansal, Gurpal S.
Dryjska, Malgorzata
Bogus, Michal
Green, Patricia
Feldmann, Marc
Brennan, Fionula
Design and Optimisation of Bioactive Cyclic Peptides: Generation of a Down-Regulator of TNF Secretion
title Design and Optimisation of Bioactive Cyclic Peptides: Generation of a Down-Regulator of TNF Secretion
title_full Design and Optimisation of Bioactive Cyclic Peptides: Generation of a Down-Regulator of TNF Secretion
title_fullStr Design and Optimisation of Bioactive Cyclic Peptides: Generation of a Down-Regulator of TNF Secretion
title_full_unstemmed Design and Optimisation of Bioactive Cyclic Peptides: Generation of a Down-Regulator of TNF Secretion
title_short Design and Optimisation of Bioactive Cyclic Peptides: Generation of a Down-Regulator of TNF Secretion
title_sort design and optimisation of bioactive cyclic peptides: generation of a down-regulator of tnf secretion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271530/
https://www.ncbi.nlm.nih.gov/pubmed/25532847
http://dx.doi.org/10.3390/molecules191221529
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