Synthesis of a novel side-chain to side-chain cyclized enkephalin analogue containing a carbonyl bridge

✍ Scribed by Danuta Pawlak; Ngoc Nga Chung; Peter W. Schiller; Jan Izdebski

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 110 KB
• Volume: 3
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/(sici)1099-1387(199707)3:4<277::aid-psc107>3.0.co;2-3

✦ Synopsis

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.