Synthesis and biological activity of homoarginine-containing opioid peptides. |
| |
Authors: | Jan Izdebski Danuta Kunce Peter W Schiller Nga N Chung Tomasz Gers Monika Zelman Monika Grabek |
| |
Affiliation: | Peptide Laboratory, Department of Chemistry, Warsaw University, Pasteura 1, Warsaw, 02-093 Poland. izdebski@chem.uw.edu.pl |
| |
Abstract: | Two tris-alkoxycarbonyl homoarginine derivatives, Boc-Har{omega,omega'-[Z(2Br)]2}-OH and Boc-Har{omega,omega'-[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. |
| |
Keywords: | dynorphin A dynorphin‐32 guanidinylation homoarginine α‐neoendorphin β‐neoendorphin opioid peptides |
|
|