THE SYNTHESIS AND OPIOID RECEPTOR-BINDING AFFINITIES OF ANALOGS OF DERMORPHIN AND ITS N-TERMINAL TETRAPEPTIDE FRAGMENT WITH DIBASIC ACIDS IN POSITION-2

Analysis of possible mu opioid receptor active conformations for dermo rphin suggested that the topographical location of the tyramine moiety of the N-terminal tyrosine can be simulated with the phenol of tyrosi ne(1) or desamino-tyrosine(1) (4-hydroxyphenylpropionic acid) and a ba sic group located on the side chain of a dibasic acid residue located in position 2. The biological properties of respective analogs with D- or L-arginine, and D- or L-lysine in the position 2 of dermorphin or desamino-dermorphin and their N-terminal tetrapeptide fragments, has p rovided evidence in support of this prediction, and questions the dogm a that an N-terminal tyrosine is a necessary element for opioid agonis t peptides.