Synthesis of a novel side-chain to side-chain cyclized enkephalin analogue containing a carbonyl bridge.
A novel type of cyclic opioid peptide analogue, cyclo[N epsilon,N epsilon'-carbonyl-D-Lys2,Lys5]enkephalinamide, was prepared from a linear precursor peptide. The peptide was synthesized on the Merrified resin and also by a combination of the solid-phase technique and the classical method in solution. In both cases the cyclization was performed by reaction of bis(4-nitrophenyl)carbonate with the free side-chain amino groups of the two lysine residues. The described method permits the convenient preparation of novel peptide analogues cyclized via a ureido group incorporating the side-chain amino groups of two alpha, omega-diamino acid residues. The cyclic enkephalin analogue containing a 21-membered ring structure showed preference for mu over delta opioid receptors in opioid bioassays in vitro.
Pawlak
D
D
Department of Chemistry, University of Warsaw, Poland.
Chung
N N
NN
Schiller
P W
PW
Izdebski
J
J
D000818:Animals; D004745:Enkephalins / Q000138:chemical synthesis* / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D014649:Vas Deferens / Q000187:drug effects
D004745:Enkephalins; C107672:enkephalinamide, cyclo(N,N'-carbonyl-lysyl(2,5))-