Development of Selective ADAMTS-5 Peptide Substrates to Monitor Proteinase Activity.


Journal

Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531

Informations de publication

Date de publication:
09 03 2023
Historique:
entrez: 9 3 2023
pubmed: 10 3 2023
medline: 11 3 2023
Statut: ppublish

Résumé

The dysregulation of proteinase activity is a hallmark of osteoarthritis (OA), a disease characterized by progressive degradation of articular cartilage by catabolic proteinases such as a disintegrin and metalloproteinase with thrombospondin type I motifs-5 (ADAMTS-5). The ability to detect such activity sensitively would aid disease diagnosis and the evaluation of targeted therapies. Förster resonance energy transfer (FRET) peptide substrates can detect and monitor disease-related proteinase activity. To date, FRET probes for detecting ADAMTS-5 activity are nonselective and relatively insensitive. We describe the development of rapidly cleaved and highly selective ADAMTS-5 FRET peptide substrates through

Identifiants

pubmed: 36891740
doi: 10.1021/acs.jmedchem.2c02090
pmc: PMC10009750
doi:

Substances chimiques

Peptides 0
Endopeptidases EC 3.4.-
ADAMTS4 Protein EC 3.4.24.82
ADAMTS5 Protein EC 3.4.24.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3522-3539

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Auteurs

Milan M Fowkes (MM)

Centre for OA Pathogenesis Versus Arthritis, Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Headington, Oxford OX3 7FY, United Kingdom.

Linda Troeberg (L)

Norwich Medical School, Bob Champion Research and Education Building, Rosalind Franklin Road, University of East Anglia, Norwich NR4 7UQ, United Kingdom.

Paul E Brennan (PE)

Alzheimer's Research UK Oxford Drug Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine Research Building, University of Oxford, Old Road Campus, Headington, Oxford OX3 7FZ, United Kingdom.

Tonia L Vincent (TL)

Centre for OA Pathogenesis Versus Arthritis, Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Headington, Oxford OX3 7FY, United Kingdom.

Morten Meldal (M)

Department of Chemistry, University of Copenhagen, Universitetsparken 5, Building B304, Copenhagen DK-2100, Denmark.

Ngee H Lim (NH)

Centre for OA Pathogenesis Versus Arthritis, Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Headington, Oxford OX3 7FY, United Kingdom.

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Classifications MeSH