Synthesis and characterization of the novel fluorescent prolyl oligopeptidase inhibitor 4-fluoresceinthiocarbamoyl-6-aminocaproyl-L-prolyl-2(S)-(hydroxyacetyl)pyrrolidine

Jarkko I Venäläinen; Erik A A Wallén; Antti Poso; J Arturo García-Horsman; Pekka T Männistö

doi:10.1021/jm0509187

Synthesis and characterization of the novel fluorescent prolyl oligopeptidase inhibitor 4-fluoresceinthiocarbamoyl-6-aminocaproyl-L-prolyl-2(S)-(hydroxyacetyl)pyrrolidine

J Med Chem. 2005 Nov 17;48(23):7093-5. doi: 10.1021/jm0509187.

Authors

Jarkko I Venäläinen¹, Erik A A Wallén, Antti Poso, J Arturo García-Horsman, Pekka T Männistö

Affiliation

¹ Department of Pharmacology and Toxicology, University of Kuopio, P.O. Box 1627, FI-70211 Kuopio, Finland. Jarkko.Venalainen@uku.fi

PMID: 16279765
DOI: 10.1021/jm0509187

Abstract

The synthesis and characterization of the first fluorescent prolyl oligopeptidase inhibitor 4-fluoresceinthiocarbamoyl-6-aminocaproyl-L-prolyl-2(S)-(hydroxyacetyl)pyrrolidine is described. This compound has an IC50 value of 0.83 nM and a dissociation half-life of 160 min, and its fluorescence signal is detectable using standard filters for fluorescein. These properties make this compound a suitable probe for visualizing prolyl oligopeptidase in various applications.

Publication types

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

MeSH terms

Dipeptides / chemical synthesis*
Dipeptides / chemistry
Fluoresceins / chemical synthesis*
Fluoresceins / chemistry
Fluorescent Dyes / chemical synthesis*
Fluorescent Dyes / chemistry
Kinetics
Peptide Hydrolases / chemistry*
Protease Inhibitors / chemical synthesis*
Protease Inhibitors / chemistry
Structure-Activity Relationship

Substances

4-fluoresceinthiocarbamoyl-6-aminocaproyl-prolyl-2-(hydroxyacetyl)pyrrolidine
Dipeptides
Fluoresceins
Fluorescent Dyes
Protease Inhibitors
Peptide Hydrolases
oligopeptidase