Dipeptidyl peptidase 9 substrates and their discovery: Current progress and the application of mass spectrometry - based approaches

Claire Wilson, Hui Zhang, Mark Gorrell, Catherine Abbott

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    Abstract

    The enzyme members of the dipeptidyl peptidase 4 (DPP4) gene family have the very unusual capacity to cleave the post-proline bond to release dipeptides from the N-terminus of peptide/protein substrates. DPP4 and related enzymes are current and potential therapeutic targets in the treatment of type II diabetes, inflammatory conditions and cancer. Despite this, the precise biological function of individual dipeptidyl peptidases (DPPs), other than DPP4, and knowledge of their in vivo substrates remains largely unknown. For many years, identification of physiological DPP substrates has been difficult due to limitations in the available tools. Now, with advances in mass spectrometry based approaches, we can discover DPP substrates on a system wide-scale. Application of these approaches has helped reveal some of the in vivo natural substrates of DPP8 and DPP9 and their unique biological roles. In this review, we provide a general overview of some tools and approaches available for protease substrate discovery and their applicability to the DPPs with a specific focus on DPP9 substrates. This review provides comment upon potential approaches for future substrate elucidation.

    Original languageEnglish
    Pages (from-to)837-856
    Number of pages20
    JournalBiological Chemistry
    Volume397
    Issue number9
    DOIs
    Publication statusPublished - 2016

    Fingerprint Dive into the research topics of 'Dipeptidyl peptidase 9 substrates and their discovery: Current progress and the application of mass spectrometry - based approaches'. Together they form a unique fingerprint.

  • Cite this