Solid phase synthesis and opioid receptor binding properties of presumable dermorphin precursor derivatives.
Presumable dermorphin precursor peptide derivatives comprised of 35 amino acids and their fragments, which are based on the amino acid sequence determined by recombinant deoxyribonucleic acid (DNA) techniques, were synthesized by the solid phase method. A 35-residue peptide amide containing L-Ala2-dermorphin sequence at the N-terminus (1) as well as its D-Ala2 isomer (2) and the C-terminal 20-residue peptide amide were found to be unexpectedly stable against aminopeptidase M digestion and in rat brain membrane fractions mixture, suggesting that the C-terminal Glu-rich moiety of 1 and 2 serves to protect from enzymatic breakdown. In the opioid receptor binding assay, 2 showed 40 and 25-fold higher affinities than 1 for mu and delta-receptors, respectively. The N-terminal 15-residue peptide fragment of 2 showed greatly increased affinities for both receptors, being one half of those of dermorphin, whereas that of 1 showed low affinities. Opioid receptor binding properties of these synthetic peptides may be useful in investigation of the processing to dermorphin.
Sasaki
Y
Y
Tohoku College of Pharmacy, Sendai, Japan.
Ambo
A
A
Suzuki
K
K
D000595:Amino Acid Sequence; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000032:analysis / Q000494:pharmacology*; D018847:Opioid Peptides; D010455:Peptides / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects*
D009842:Oligopeptides; D018847:Opioid Peptides; D010455:Peptides; D011957:Receptors, Opioid; C030058:dermorphin