Synthesis and biological activity of homoarginine-containing opioid peptides.
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.
Izdebski
Jan
J
Peptide Laboratory, Department of Chemistry, Warsaw University, Pasteura 1, Warsaw, 02-093 Poland. izdebski@chem.uw.edu.pl
Kunce
Danuta
D
Schiller
Peter W
PW
Chung
Nga N
NN
Gers
Tomasz
T
Zelman
Monika
M
Grabek
Monika
M
D000595:Amino Acid Sequence; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006709:Homoarginine / Q000737:chemistry*; D007082:Ileum / Q000187:drug effects; D008297:Male; D051379:Mice; D018847:Opioid Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014649:Vas Deferens / Q000187:drug effects
D018847:Opioid Peptides; D006709:Homoarginine