Novel selective inhibitors of aminopeptidases that generate antigenic peptides

Athanasios Papakyriakou; Efthalia Zervoudi; Emmanuel A Theodorakis; Loredana Saveanu; Efstratios Stratikos; Dionisios Vourloumis

doi:10.1016/j.bmcl.2013.07.024

Novel selective inhibitors of aminopeptidases that generate antigenic peptides

Bioorg Med Chem Lett. 2013 Sep 1;23(17):4832-6. doi: 10.1016/j.bmcl.2013.07.024. Epub 2013 Jul 23.

Authors

Athanasios Papakyriakou¹, Efthalia Zervoudi, Emmanuel A Theodorakis, Loredana Saveanu, Efstratios Stratikos, Dionisios Vourloumis

Affiliation

¹ Department of Chemistry & Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA.

PMID: 23916253
DOI: 10.1016/j.bmcl.2013.07.024

Abstract

Endoplasmic reticulum aminopeptidases, ERAP1 and ERAP2, as well as Insulin regulated aminopeptidase (IRAP) play key roles in antigen processing, and have recently emerged as biologically important targets for manipulation of antigen presentation. Taking advantage of the available structural and substrate-selectivity data for these enzymes, we have rationally designed a new series of inhibitors that display low micromolar activity. The selectivity profile for these three highly homologous aminopeptidases provides a promising avenue for modulating intracellular antigen processing.

Keywords: ERAP1; ERAP2; Endoplasmic reticulum aminopeptidase; IRAP; Molecular modeling; Rational design; Selective inhibitor.

Publication types

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

MeSH terms

Aminopeptidases / antagonists & inhibitors*
Cystinyl Aminopeptidase / antagonists & inhibitors*
Drug Design
Endoplasmic Reticulum / enzymology*
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology*
Humans
Models, Molecular

Substances

Enzyme Inhibitors
Aminopeptidases
Cystinyl Aminopeptidase
leucyl-cystinyl aminopeptidase