DALDA analogues containing alpha-hydroxymethylamino acids.
To evaluate the role of aromatic amino-acids residues, four analogues of the mu-selective opioid peptide agonist DALDA (H-Tyr-D-Arg-Phe-Lys-NH2) containing the amphiphilic, a,a-disubstituted amino acid (R)- or (S)-alpha-hydroxymethyltyrosine (HmTyr) in position 1 and (R)- or (S)-alpha-hydroxymethylphenylalanine (HmPhe) in position 3 of the peptide sequence were synthesized. Only the [(R)-HmPhe3)]DALDA analogue displayed full agonistic activity in both the guinea pig ileum and the mouse vas deferens assays and turned out to be a delta receptor-selective opioid agonist.
Olma
A
A
Institute of Organic Chemistry, Technical University of Lódź, Poland.
Chung
N N
NN
Schiller
P W
PW
Zabrocki
J
J
D000596:Amino Acids / Q000737:chemistry*; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism; D008297:Male; D009842:Oligopeptides / Q000737:chemistry*; D018847:Opioid Peptides / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry*; D014649:Vas Deferens / Q000378:metabolism
D000596:Amino Acids; D000700:Analgesics; D009842:Oligopeptides; D018847:Opioid Peptides; D010455:Peptides; C063076:tyrosyl-arginyl-phenylalanyl-lysinamide; C092680:4-hydroxymethylphenylalanine; D014443:Tyrosine; D010649:Phenylalanine; C008054:3-(hydroxymethyl)tyrosine