In vivo imaging of MMP‐13 activity using a specific polymer‐FRET peptide conjugate detects early osteoarthritis and inhibitor efficacy
Imaging early molecular changes in osteoarthritic (OA) joints is instrumental for the development of disease‐modifying drugs. To this end, a fluorescent resonance energy transfer‐based peptide probe that is cleavable by matrix metalloproteinase 13 (MMP‐13) has been developed. This protease degrades...
Main Authors: | , , , , , , , , , , , , |
---|---|
Format: | Journal article |
Published: |
Wiley
2018
|
_version_ | 1797100651140874240 |
---|---|
author | Duro‐Castano, A Lim, N Tranchant, I Amoura, M Beau, F Wieland, H Kingler, O Herrmann, M Nazaré, M Plettenburg, O Dive, V Vicent, M Nagase, H |
author_facet | Duro‐Castano, A Lim, N Tranchant, I Amoura, M Beau, F Wieland, H Kingler, O Herrmann, M Nazaré, M Plettenburg, O Dive, V Vicent, M Nagase, H |
author_sort | Duro‐Castano, A |
collection | OXFORD |
description | Imaging early molecular changes in osteoarthritic (OA) joints is instrumental for the development of disease‐modifying drugs. To this end, a fluorescent resonance energy transfer‐based peptide probe that is cleavable by matrix metalloproteinase 13 (MMP‐13) has been developed. This protease degrades type II collagen, a major matrix component of cartilage. The probe exhibits high catalytic efficiency (kcat/KM = 6.5 × 105m−1 s−1) and high selectivity for MMP‐13 over a set of nine MMPs. To achieve optimal in vivo pharmacokinetics and tissue penetration, the probe has been further conjugated to a linear l‐polyglutamate chain of 30 kDa. The conjugate detects early biochemical events that occur in a surgically induced murine model of OA before major histological changes. The nanometric probe is suitable for the monitoring of in vivo efficacy of an orally bioavailable MMP‐13 inhibitor, which effectively blocks cartilage degradation during the development of OA. This new polymer‐probe can therefore be a useful tool in detecting early OA, disease progression, and in developing MMP‐13‐based disease‐modifying drugs for OA. |
first_indexed | 2024-03-07T05:40:36Z |
format | Journal article |
id | oxford-uuid:e5704005-e7fc-4dba-9208-448226592a9b |
institution | University of Oxford |
last_indexed | 2024-03-07T05:40:36Z |
publishDate | 2018 |
publisher | Wiley |
record_format | dspace |
spelling | oxford-uuid:e5704005-e7fc-4dba-9208-448226592a9b2022-03-27T10:23:55ZIn vivo imaging of MMP‐13 activity using a specific polymer‐FRET peptide conjugate detects early osteoarthritis and inhibitor efficacyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e5704005-e7fc-4dba-9208-448226592a9bSymplectic Elements at OxfordWiley2018Duro‐Castano, ALim, NTranchant, IAmoura, MBeau, FWieland, HKingler, OHerrmann, MNazaré, MPlettenburg, ODive, VVicent, MNagase, HImaging early molecular changes in osteoarthritic (OA) joints is instrumental for the development of disease‐modifying drugs. To this end, a fluorescent resonance energy transfer‐based peptide probe that is cleavable by matrix metalloproteinase 13 (MMP‐13) has been developed. This protease degrades type II collagen, a major matrix component of cartilage. The probe exhibits high catalytic efficiency (kcat/KM = 6.5 × 105m−1 s−1) and high selectivity for MMP‐13 over a set of nine MMPs. To achieve optimal in vivo pharmacokinetics and tissue penetration, the probe has been further conjugated to a linear l‐polyglutamate chain of 30 kDa. The conjugate detects early biochemical events that occur in a surgically induced murine model of OA before major histological changes. The nanometric probe is suitable for the monitoring of in vivo efficacy of an orally bioavailable MMP‐13 inhibitor, which effectively blocks cartilage degradation during the development of OA. This new polymer‐probe can therefore be a useful tool in detecting early OA, disease progression, and in developing MMP‐13‐based disease‐modifying drugs for OA. |
spellingShingle | Duro‐Castano, A Lim, N Tranchant, I Amoura, M Beau, F Wieland, H Kingler, O Herrmann, M Nazaré, M Plettenburg, O Dive, V Vicent, M Nagase, H In vivo imaging of MMP‐13 activity using a specific polymer‐FRET peptide conjugate detects early osteoarthritis and inhibitor efficacy |
title | In vivo imaging of MMP‐13 activity using a specific polymer‐FRET peptide conjugate detects early osteoarthritis and inhibitor efficacy |
title_full | In vivo imaging of MMP‐13 activity using a specific polymer‐FRET peptide conjugate detects early osteoarthritis and inhibitor efficacy |
title_fullStr | In vivo imaging of MMP‐13 activity using a specific polymer‐FRET peptide conjugate detects early osteoarthritis and inhibitor efficacy |
title_full_unstemmed | In vivo imaging of MMP‐13 activity using a specific polymer‐FRET peptide conjugate detects early osteoarthritis and inhibitor efficacy |
title_short | In vivo imaging of MMP‐13 activity using a specific polymer‐FRET peptide conjugate detects early osteoarthritis and inhibitor efficacy |
title_sort | in vivo imaging of mmp 13 activity using a specific polymer fret peptide conjugate detects early osteoarthritis and inhibitor efficacy |
work_keys_str_mv | AT durocastanoa invivoimagingofmmp13activityusingaspecificpolymerfretpeptideconjugatedetectsearlyosteoarthritisandinhibitorefficacy AT limn invivoimagingofmmp13activityusingaspecificpolymerfretpeptideconjugatedetectsearlyosteoarthritisandinhibitorefficacy AT tranchanti invivoimagingofmmp13activityusingaspecificpolymerfretpeptideconjugatedetectsearlyosteoarthritisandinhibitorefficacy AT amouram invivoimagingofmmp13activityusingaspecificpolymerfretpeptideconjugatedetectsearlyosteoarthritisandinhibitorefficacy AT beauf invivoimagingofmmp13activityusingaspecificpolymerfretpeptideconjugatedetectsearlyosteoarthritisandinhibitorefficacy AT wielandh invivoimagingofmmp13activityusingaspecificpolymerfretpeptideconjugatedetectsearlyosteoarthritisandinhibitorefficacy AT kinglero invivoimagingofmmp13activityusingaspecificpolymerfretpeptideconjugatedetectsearlyosteoarthritisandinhibitorefficacy AT herrmannm invivoimagingofmmp13activityusingaspecificpolymerfretpeptideconjugatedetectsearlyosteoarthritisandinhibitorefficacy AT nazarem invivoimagingofmmp13activityusingaspecificpolymerfretpeptideconjugatedetectsearlyosteoarthritisandinhibitorefficacy AT plettenburgo invivoimagingofmmp13activityusingaspecificpolymerfretpeptideconjugatedetectsearlyosteoarthritisandinhibitorefficacy AT divev invivoimagingofmmp13activityusingaspecificpolymerfretpeptideconjugatedetectsearlyosteoarthritisandinhibitorefficacy AT vicentm invivoimagingofmmp13activityusingaspecificpolymerfretpeptideconjugatedetectsearlyosteoarthritisandinhibitorefficacy AT nagaseh invivoimagingofmmp13activityusingaspecificpolymerfretpeptideconjugatedetectsearlyosteoarthritisandinhibitorefficacy |