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New strategies for targeting matrix metalloproteinases

The development of matrix metalloproteinase (MMP) inhibitors has often been frustrated by a lack of specificity and subsequent off-target effects. More recently, inhibitor design has considered secondary binding sites (exosites) to improve specificity. Small molecules and peptides have been develope...

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Detalles Bibliográficos
Autor principal: Fields, Gregg B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466128/
https://www.ncbi.nlm.nih.gov/pubmed/25595836
http://dx.doi.org/10.1016/j.matbio.2015.01.002
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author Fields, Gregg B.
author_facet Fields, Gregg B.
author_sort Fields, Gregg B.
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description The development of matrix metalloproteinase (MMP) inhibitors has often been frustrated by a lack of specificity and subsequent off-target effects. More recently, inhibitor design has considered secondary binding sites (exosites) to improve specificity. Small molecules and peptides have been developed that bind exosites in the catalytic (CAT) domain of MMP-13, the CAT or hemopexin-like (HPX) domain of MT1-MMP, and the collagen binding domain (CBD) of MMP-2 and MMP-9. Antibody-based approaches have resulted in selective inhibitors for MMP-9 and MT1-MMP that target CAT domain exosites. Triple-helical “mini-proteins” have taken advantage of collagen binding exosites, producing a family of novel probes. A variety of non-traditional approaches that incorporate exosite binding into the design process has yielded inhibitors with desirable selectivities within the MMP family.
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spelling pubmed-44661282015-06-15 New strategies for targeting matrix metalloproteinases Fields, Gregg B. Matrix Biol Article The development of matrix metalloproteinase (MMP) inhibitors has often been frustrated by a lack of specificity and subsequent off-target effects. More recently, inhibitor design has considered secondary binding sites (exosites) to improve specificity. Small molecules and peptides have been developed that bind exosites in the catalytic (CAT) domain of MMP-13, the CAT or hemopexin-like (HPX) domain of MT1-MMP, and the collagen binding domain (CBD) of MMP-2 and MMP-9. Antibody-based approaches have resulted in selective inhibitors for MMP-9 and MT1-MMP that target CAT domain exosites. Triple-helical “mini-proteins” have taken advantage of collagen binding exosites, producing a family of novel probes. A variety of non-traditional approaches that incorporate exosite binding into the design process has yielded inhibitors with desirable selectivities within the MMP family. 2015-01-14 2015 /pmc/articles/PMC4466128/ /pubmed/25595836 http://dx.doi.org/10.1016/j.matbio.2015.01.002 Text en © 2015 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Fields, Gregg B.
New strategies for targeting matrix metalloproteinases
title New strategies for targeting matrix metalloproteinases
title_full New strategies for targeting matrix metalloproteinases
title_fullStr New strategies for targeting matrix metalloproteinases
title_full_unstemmed New strategies for targeting matrix metalloproteinases
title_short New strategies for targeting matrix metalloproteinases
title_sort new strategies for targeting matrix metalloproteinases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466128/
https://www.ncbi.nlm.nih.gov/pubmed/25595836
http://dx.doi.org/10.1016/j.matbio.2015.01.002
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