DALDA analogues containing -hydroxymethylamino acids
نویسندگان
چکیده
To evaluate the role of aromatic amino-acids residues, four analogues of the -selective opioid peptide agonist DALDA (H-Tyr-D-Arg-Phe-Lys-NH2) containing the amphiphilic, , -disubstituted amino acid (R)or (S)-hydroxymethyltyrosine (HmTyr) in position 1 and (R)or (S)-hydroxymethylphenylalanine (HmPhe) in position 3 of the peptide sequence were synthesized. Only the [(R)-HmPhe 3 )]DALDA analogue displayed full agonistic activity in both the guinea pig ileum and the mouse vas deferens assays and turned out to be a receptor-selective opioid agonist.
منابع مشابه
Dansylated analogues of the opioid peptide [Dmt1]DALDA: in vitro activity profiles and fluorescence parameters.
Dansylated analogues of the potent and selective micro opioid peptide agonist [Dmt(1)]DALDA (H-Dmt-D-Arg-Phe-Lys-NH(2); Dmt = 2',6'-dimethyltyrosine) were prepared either by substitution of N(beta)-dansyl-alpha,beta-diaminopropionic acid or N(epsilon)-dansyllysine for Lys(4), or by attachment of a dansyl group to the C-terminal carboxamide function via a linker. All three analogues displayed hi...
متن کاملAntinociceptive and respiratory effects of intrathecal H-Tyr-D-Arg-Phe-Lys-NH2 (DALDA) and [Dmt1] DALDA.
DALDA (H-Tyr-D-Arg-Phe-Lys-NH(2)) and [Dmt(1)]DALDA (H-Dmt-D-Arg-Phe-Lys-NH(2)) (Dmt = 2',6'-dimethyltyrosine) are potent and highly selective mu-opioid agonists (K(i)(delta)/K(i)(mu) > 10,000 and K(i)(kappa)/K(i)(mu) > 100). Both peptides carry a 3+ charge at physiological pH. Their antinociceptive and respiratory effects were compared with morphine (MOR) after intrathecal administration in ra...
متن کاملIn vivo pharmacokinetics of selective mu-opioid peptide agonists.
Recent evidence suggests that highly selective mu-opioid agonists may provide good analgesia with less development of tolerance and dependence. H-Tyr-D-Arg-Phe-Lys-NH2 (DALDA) and H-Dmt-D-Arg-Phe-Lys-NH2 ([Dmt1]DALDA) were found to display high binding affinity and much greater selectivity for the mu-opioid receptor (K(i)delta/K(i)mu) > 10,000) compared with H-Tyr-D-Ala-Gly-MePhe-Gly-ol (DAMGO)...
متن کاملEndogenous opioid peptides contribute to antinociceptive potency of intrathecal [Dmt1]DALDA.
[Dmt(1)]DALDA (H-Dmt-d-Arg-Phe-Lys-NH(2); Dmt = 2',6'-dimethyltyrosine) is a dermorphin analog that shows high affinity and selectivity for the mu opioid receptor. The intrathecal potency of [Dmt(1)]DALDA far exceeded its affinity at mu receptors and suggests that other mechanisms must be involved in its action in the spinal cord. The affinity and selectivity of [Dmt(1)]DALDA was determined usi...
متن کاملIn vivo disposition of dermorphin analog (DALDA) in nonpregnant and pregnant sheep.
Although synthetic opioid peptide analogs have been used extensively to study the functional roles of opioid receptors, little is known about their in vivo disposition. Our goal was to develop novel opioid drugs with limited transfer across the placenta. DALDA (Tyr-D-Arg-Phe-Lys-NH2) is a potent and highly selective mu agonist that is quite polar because of its 3+ charge at physiological pH. It...
متن کامل