PuSH - Publication Server of Helmholtz Zentrum München: <em>In vivo</em> imaging of MMP-13 activity using a specific polymer-FRET peptide conjugate detects early osteoarthritis and inhibitor efficacy.

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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)

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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.

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