Inhibition of prolyl oligopeptidase with a synthetic unnatural dipeptide

Daugirdas Tomas Racys; Dean Rea; Vilmos Fülöp; Martin Wills

doi:10.1016/j.bmc.2010.05.012

Inhibition of prolyl oligopeptidase with a synthetic unnatural dipeptide

Bioorg Med Chem. 2010 Jul 1;18(13):4775-82. doi: 10.1016/j.bmc.2010.05.012. Epub 2010 May 31.

Authors

Daugirdas Tomas Racys¹, Dean Rea, Vilmos Fülöp, Martin Wills

Affiliation

¹ Department of Chemistry, The University of Warwick, Coventry CV47AL, UK.

PMID: 20627594
DOI: 10.1016/j.bmc.2010.05.012

Abstract

A new inhibitor, containing a linked proline-piperidine structure, for the enzyme prolyl oligopeptidase (POP) has been synthesised and demonstrated to bind covalently with the enzyme at the active site. This provides evidence that covalent inhibitors of POP do not have to be limited to structures containing five-membered N-containing heterocyclic rings.

Publication types

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

MeSH terms

Binding Sites
Catalytic Domain
Crystallography, X-Ray
Dipeptides / chemical synthesis
Dipeptides / chemistry*
Dipeptides / pharmacology
Proline / chemistry
Prolyl Oligopeptidases
Pyrrolidines / chemistry
Serine Endopeptidases / chemistry*
Serine Endopeptidases / metabolism
Serine Proteinase Inhibitors / chemical synthesis
Serine Proteinase Inhibitors / chemistry*
Serine Proteinase Inhibitors / pharmacology

Substances

Dipeptides
Pyrrolidines
Serine Proteinase Inhibitors
Proline
Serine Endopeptidases
Prolyl Oligopeptidases