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 mu opioid receptor active conformations for dermorphin suggested that the topographical location of the tyramine moiety of the N-terminal tyrosine can be simulated with the phenol of tyrosine or desamino-tyrosine (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 desamino-dermorphin 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.
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D000701:Analgesics, Opioid / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D001681:Biological Assay; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism* / Q000494:pharmacology; D018847:Opioid Peptides; D010455:Peptides / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D014439:Tyramine / Q000737:chemistry
D000596:Amino Acids; D000701:Analgesics, Opioid; D009842:Oligopeptides; D018847:Opioid Peptides; D010455:Peptides; D017450:Receptors, Opioid, mu; C030058:dermorphin; D014439:Tyramine