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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2014
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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. |
format | Online Article Text |
id | pubmed-6271530 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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