The synthesis and opioid receptor binding affinities of analogues of dermorphin and its N-terminal tetrapeptide fragment with dibasic acids in position 2

Analysis of possible μ opioid receptor active conformations for dermorphin suggested that the topographical location of the tyramine moiety of the N-tenninal tyrosine can be simulated with the phenol of tyrosine¹ or desamino-tyrosine¹ (4-hydroxyphenylpropionic acid) and a basic 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 desaminodermorphin and their N-terminal tetrapeptide fragments, has provided evidence in support of this prediction, and questions the dogma that an N-terminal tyrosine is a necessary element for opioid agonist peptides.