Duro-Castano, A.* ; Lim, N.H.* ; Tranchant, I.* ; Amoura, M.* ; Beau, F.* ; Wieland, H.* ; Kingler, O.* ; Hermann, M.* ; Nazaré, M.* ; Plettenburg, O. ; Dive, V.* ; Vicent, M.J.* ; Nagase, H.*
In vivo imaging of MMP-13 activity using a specific polymer-FRET peptide conjugate detects early osteoarthritis and inhibitor efficacy.
Adv. Func. Mat. 28:1802738 (2018)
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 (k(cat)/K-M = 6.5 x 10(5) m(-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.
Impact Factor
Scopus SNIP
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Times Cited
Scopus
Cited By
Altmetric
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Early Detection ; Live Imaging ; Mmp-13 Nanoprobes ; Osteoarthritis ; Polymer Therapeutics; Matrix-metalloproteinase; Cartilage Degradation; Selective-inhibition; Articular-cartilage; Mouse Model; Probes; Discovery; Proteases; Collagen; Therapy
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2018
Prepublished im Jahr
HGF-Berichtsjahr
2018
ISSN (print) / ISBN
1616-301X
e-ISSN
1616-3028
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 28,
Heft: 37,
Seiten: ,
Artikelnummer: 1802738
Supplement: ,
Reihe
Verlag
Wiley
Verlagsort
Weinheim
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Medicinal Chemistry (IMC)
POF Topic(s)
30203 - Molecular Targets and Therapies
Forschungsfeld(er)
Enabling and Novel Technologies
PSP-Element(e)
G-506300-001
Förderungen
Copyright
Erfassungsdatum
2018-09-24