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Pseudopeptide analogues of the delta opioid antagonists H-Tyr-Tic-Phe-Phe-OH (TIPP) and H-Tyr-Tic-Phe-OH (TIP) containing a reduced peptide bond between the Tic2 and Phe3 residues were synthesized. The two compounds, H-Tyr-Tic psi [CH2NH]Phe-Phe-OH (TIPP [psi]) and H-Tyr-Tic psi-[CH2NH]Phe-OH (TIP [psi]), were tested in mu-, delta-, and(More)
Opioid peptide analogs consisting entirely of aromatic amino acid residues and containing conformationally restricted phenylalanine derivatives in position 2 of the peptide sequence were synthesized and pharmacologically characterized in vitro. Both diastereoisomers of H-Tyr-(D or L)-NMePhe-Phe-Phe-NH2 (NMePhe is N alpha-methylphenylalanine) were(More)
The tetrapeptide DALDA (H-Tyr-D-Arg-Phe-Lys-NH2) is a polar and selective mu agonist showing poor penetration of the placental and blood-brain barriers. In an effort to enhance the potency of DALDA, analogues containing 2',6'-dimethyltyrosine (Dmt), N,2',6'-trimethyltyrosine (Tmt), 2'-methyltyrosine (Mmt) or 2'-hydroxy,6'-methyltyrosine (Hmt) in place of(More)
Opioid compounds with mixed mu agonist/delta antagonist properties are expected to be analgesics with low propensity to produce tolerance and dependence. In an effort to strengthen the mu agonist component of the mixed mu agonist/delta antagonist H-Tyr-Tic-Phe-Phe-NH(2) (TIPP-NH(2)), analogues containing structurally modified tyrosine residues in place of(More)
According to the membrane compartment concept the receptor specificity of ligands is based not only on ligand-receptor complementarity but also on specific ligand-membrane interactions. Elaboration of this concept for opioid peptide-receptor interactions had led to the assumption that mu- and delta-receptors are located in anionic and cationic membrane(More)
The discovery of the prototype delta opioid antagonists TIPP (H-Tyr-Tic-Phe-Phe-OH) and TIP (H-Tyr-Tic-Phe-OH) in 1992 was followed by extensive structure-activity relationship studies, leading to the development of analogues that are of interest as pharmacological tools or as potential therapeutic agents. Stable TIPP-derived delta opioid antagonists with(More)
Recent studies showed that dermorphin and enkephalin analogues containing two methyl groups at the 2',6'-positions of the Tyr(1) aromatic ring and lacking an N-terminal amino group were moderately potent delta and mu opioid antagonists. These results indicate that a positively charged N-terminal amino group may be essential for signal transduction but not(More)
Using a combination of solid-phase and solution methods, we synthesized a series of cyclic [Leu5]enkephalin analogues by substitution of D-alpha, omega-diamino acids in position 2 of the enkephalin sequence and cyclization of the omega-amino group to the C-terminal carboxy group of leucine. Cyclic analogues containing D-alpha, beta-diaminopropionic acid(More)
Analogues of the opioid peptides [D-Phe(3)]morphiceptin (H-Tyr-Pro-D-Phe-Pro-NH(2)) and endomorphin-2 (H-Tyr-Pro-Phe-Phe-NH(2)) containing the pseudoproline (Psi Pro) (4R)-thiazolidine-4-carboxylic acid (Cys[Psi(R1,R2)pro]) or (4S)-oxazolidine-4-carboxylic acid (Ser[Psi(R1,R2)pro]) in place of Pro(2) were synthesized. The pseudoproline ring in these(More)
Two dermorphin analogues having an almost identical structure but different structural flexibility were compared for opioid activity. In 1 the aromatic side chains were incorporated into a lactam structure, while in 2 N-amide alkylation was retained but the side chains were flexible. Both compounds produced comparable antinociceptive effects in the mouse(More)