Izdebski Jan, Kunce Danuta, Schiller Peter W, Chung Nga N, Gers Tomasz, Zelman Monika, Grabek Monika
Peptide Laboratory, Department of Chemistry, Warsaw University, Pasteura 1, Warsaw, 02-093 Poland.
J Pept Sci. 2007 Jan;13(1):27-30. doi: 10.1002/psc.785.
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.
通过对Boc-Lys-OH进行胍基化反应制备了两种三烷氧基羰基高精氨酸衍生物，即Boc-Har{ω,ω'-[Z(2Br)]2}-OH和Boc-Har{ω,ω'-[Z(2Cl)]2}-OH，并将其用于新内啡肽和强啡肽的合成。将结果与在肽链中引入Boc-Lys(Fmoc)-OH，去除Fmoc保护后，用N,N'-[Z(2Br)]2-或N,N'-[Z(2Cl)]2-S-甲基异脲对所得肽树脂进行胍基化反应的合成结果进行了比较。在豚鼠回肠（GPI）和小鼠输精管（MVD）试验中对这些肽进行了测试。结果表明，用高精氨酸取代精氨酸可能是设计对类胰蛋白酶降解具有更高抗性的生物活性肽的一条良好途径。
