A novel type of cyclic opiod peptide analogue, cyclo(N e ,N e H -carbonyl-D-Lys 2 ,Lys 5 )enkephalinamide, was prepared from a linear precursor peptide. The peptide was synthesized on the Merrifield 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 a,o-diamino acid residues. The cyclic enkephalin analogue containing a 21-membered ring structure showed preference for m over d opioid
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