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Rational Design of MMP Degradable Peptide-Based Supramolecular Filaments

[Image: see text] One-dimensional nanostructures formed by self-assembly of small molecule peptides have been extensively explored for use as biomaterials in various biomedical contexts. However, unlike individual peptides that can be designed to be specifically degradable by enzymes/proteases of in...

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Autores principales: Lin, Yi-An, Ou, Yu-Chuan, Cheetham, Andrew G., Cui, Honggang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3993905/
https://www.ncbi.nlm.nih.gov/pubmed/24611531
http://dx.doi.org/10.1021/bm500020j
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author Lin, Yi-An
Ou, Yu-Chuan
Cheetham, Andrew G.
Cui, Honggang
author_facet Lin, Yi-An
Ou, Yu-Chuan
Cheetham, Andrew G.
Cui, Honggang
author_sort Lin, Yi-An
collection PubMed
description [Image: see text] One-dimensional nanostructures formed by self-assembly of small molecule peptides have been extensively explored for use as biomaterials in various biomedical contexts. However, unlike individual peptides that can be designed to be specifically degradable by enzymes/proteases of interest, their self-assembled nanostructures, particularly those rich in β-sheets, are generally resistant to enzymatic degradation because the specific cleavage sites are often embedded inside the nanostructures. We report here on the rational design of β-sheet rich supramolecular filaments that can specifically dissociate into less stable micellar assemblies and monomers upon treatment with matrix metalloproteases-2 (MMP-2). Through linkage of an oligoproline segment to an amyloid-derived peptide sequence, we first synthesized an amphiphilic peptide that can undergo a rapid morphological transition in response to pH variations. We then used MMP-2 specific peptide substrates as multivalent cross-linkers to covalently fix the amyloid-like filaments in the self-assembled state at pH 4.5. Our results show that the cross-linked filaments are stable at pH 7.5 but gradually break down into much shorter filaments upon cleavage of the peptidic cross-linkers by MMP-2. We believe that the reported work presents a new design platform for the creation of amyloid-like supramolecular filaments responsive to enzymatic degradation.
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spelling pubmed-39939052015-03-10 Rational Design of MMP Degradable Peptide-Based Supramolecular Filaments Lin, Yi-An Ou, Yu-Chuan Cheetham, Andrew G. Cui, Honggang Biomacromolecules [Image: see text] One-dimensional nanostructures formed by self-assembly of small molecule peptides have been extensively explored for use as biomaterials in various biomedical contexts. However, unlike individual peptides that can be designed to be specifically degradable by enzymes/proteases of interest, their self-assembled nanostructures, particularly those rich in β-sheets, are generally resistant to enzymatic degradation because the specific cleavage sites are often embedded inside the nanostructures. We report here on the rational design of β-sheet rich supramolecular filaments that can specifically dissociate into less stable micellar assemblies and monomers upon treatment with matrix metalloproteases-2 (MMP-2). Through linkage of an oligoproline segment to an amyloid-derived peptide sequence, we first synthesized an amphiphilic peptide that can undergo a rapid morphological transition in response to pH variations. We then used MMP-2 specific peptide substrates as multivalent cross-linkers to covalently fix the amyloid-like filaments in the self-assembled state at pH 4.5. Our results show that the cross-linked filaments are stable at pH 7.5 but gradually break down into much shorter filaments upon cleavage of the peptidic cross-linkers by MMP-2. We believe that the reported work presents a new design platform for the creation of amyloid-like supramolecular filaments responsive to enzymatic degradation. American Chemical Society 2014-03-10 2014-04-14 /pmc/articles/PMC3993905/ /pubmed/24611531 http://dx.doi.org/10.1021/bm500020j Text en Copyright © 2014 American Chemical Society
spellingShingle Lin, Yi-An
Ou, Yu-Chuan
Cheetham, Andrew G.
Cui, Honggang
Rational Design of MMP Degradable Peptide-Based Supramolecular Filaments
title Rational Design of MMP Degradable Peptide-Based Supramolecular Filaments
title_full Rational Design of MMP Degradable Peptide-Based Supramolecular Filaments
title_fullStr Rational Design of MMP Degradable Peptide-Based Supramolecular Filaments
title_full_unstemmed Rational Design of MMP Degradable Peptide-Based Supramolecular Filaments
title_short Rational Design of MMP Degradable Peptide-Based Supramolecular Filaments
title_sort rational design of mmp degradable peptide-based supramolecular filaments
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3993905/
https://www.ncbi.nlm.nih.gov/pubmed/24611531
http://dx.doi.org/10.1021/bm500020j
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