These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Dipeptide proline diphenyl phosphonates are potent, irreversible inhibitors of seprase (FAPalpha).
    Author: Gilmore BF, Lynas JF, Scott CJ, McGoohan C, Martin L, Walker B.
    Journal: Biochem Biophys Res Commun; 2006 Jul 28; 346(2):436-46. PubMed ID: 16769036.
    Abstract:
    Dipeptidyl peptidase IV (DPP-IV) and seprase belong to a small group of membrane-bound, proline-specific serine proteases, the serine integral membrane proteases (SIMPs). Whilst DPP-IV is the most exhaustively studied peptidase in this class, relatively less is known about the inhibitor/substrate specificity of its close homolog seprase. Additionally, whereas, DPP-IV expression is largely ubiquitous, seprase expression is restricted to tumour and tissue remodelling sites in vivo. Consequently, the highly restricted expression and distribution of seprase potentially make it an excellent therapeutic target for the modulation of neoplastic invasion and metastasis. Against this background, we now wish to report on the design, synthesis, and kinetic testing of a series of dipeptide proline diphenyl phosphonates, against DPP-IV and seprase. The most potent inhibitor of DPP-IV and seprase was found to be Gly-ProP(OPh)2, which exhibited overall second-order rate constants of inactivation of 5.24 x 105 M-1 min-1 and 1.06 x 104 M-1 min-1 against DPP-IV and seprase, respectively. Both proteases displayed differing profiles of susceptibility towards the other members of the series of inhibitors synthesised. In addition, Gly-ProP(OPh)2 and Tyr-ProP(OPh)2 were found to exert a considerable, dose-dependent anti-invasive effect on the LOX melanoma cell line, in vitro.
    [Abstract] [Full Text] [Related] [New Search]