Synthesis and biological activity of homoarginine-containing opioid peptides - Biologics Delivery

Synthesis and biological activity of homoarginine-containing opioid peptides
Received: 12 June 2006; Accepted: 25 June 2006
Jan Izdebski 1 *, Danuta Kunce 1, Peter W. Schiller 2, Nga N. Chung 2, Tomasz Gers 1, Monika Zelman 1, Monika Grabek 1
Journal of Peptide Science
Published Online: 11 Sep 2006
Wiley InterScience
Copyright ? 2006 European Peptide Society and John Wiley & Sons, Ltd.
1Peptide Laboratory, Department of Chemistry, Warsaw University, Pasteura 1, Warsaw, 02-093 Poland
2Laboratory of Chemical Biology and Peptide Research, Clinical Research Institute of Montreal, Montreal, H2W IR7 Quebec, Canada

email: Jan Izdebski (izdebski@chem.uw.edu.pl)
*Correspondence to Jan Izdebski, Peptide Laboratory, Department of Chemistry, Warsaw University, Pasteura 1, 02-093 Warsaw, Poland
Funded by:
Ministry of Science and Informatics, Poland; Grant Number: 3T09A 023 28
CIHR; Grant Number: MOP-5655
NIH; Grant Number: DA-04443
Keywords
dynorphin A ? dynorphin-32 ? guanidinylation ? homoarginine ? -neoendorphin ? -neoendorphin ? opioid peptides
Abstract
Two tris-alkoxycarbonyl homoarginine derivatives, Boc-Har{,-[Z(2Br)]2}-OH and Boc-Har{,-[Z(2Cl)]2}-OH, were prepared by guanidinylation of Boc-Lys-OH, and used for the synthesis of neo-endorphins and dynorphins. The results were compared with that obtained in the synthesis in which Boc-Lys(Fmoc)-OH was incorporated into the peptide chain, and after removing Fmoc protection, the resulting peptide-resin was guanidinylated with N,N-[Z(2Br)]2- or N,N-[Z(2Cl)]2-S-methylisourea. The peptides were tested in the guinea-pig ileum (GPI) and mouse vas deferens (MVD) assays. The results indicated that replacement of Arg by Har may be a good avenue for the design of biologically active peptides with increased resistance to degradation by trypsin-like enzymes. Copyright ? 2006 European Peptide Society and John Wiley & Sons, Ltd.
You can view the abstract online. A subscription is required to view the full text or it can be purchased online.