Carole Lemieux

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A series of deltorphin I analogs containing D- or L-N-methylalanine (MeAla), D- or L-proline (Pro), alpha-aminoisobutyric acid (Aib), sarcosine (Sar) or D-tert-leucine (Tle) in place of D-Ala2, or phenylalanine in place of Tyr1, was synthesized. The opioid activity profiles of these peptides were determined in mu and delta opioid receptor-representative(More)
Bivalent ligands consisting of oxymorphamine and [D-Glu2]enkephalin pharmacophores linked through a spacer attached to the 6-amino group of the former and D-Glu of the latter were synthesized in an effort to investigate the possible coexistence of mu and delta recognition sites in the same opioid receptor complex. Of the two bivalent ligands (1,2)(More)
A screening of conformationally constrained aromatic amino acids as base cores for the preparation of new NK1 receptor antagonists resulted in the discovery of three new NK1 receptor antagonists, 19 [Ac-Aba-Gly-NH-3',5'-(CF(3))(2)-Bn], 20 [Ac-Aba-Gly-NMe-3',5'-(CF(3))(2)-Bn], and 23 [Ac-Tic-NMe-3',5'-(CF(3))(2)-Bn], which were able to counteract the agonist(More)
H-Dmt-D-Arg-Phe-Lys-NH2 (Dmt=2',6'-dimethyltyrosine) ([Dmt1] DALDA) is a highly potent and selective micro opioid peptide agonist capable of producing an antinociceptive effect after systemic administration. Fluorescent analogues of [Dmt1] DALDA containing either beta-dansyl-L-alpha,beta-diaminopropionic acid [Dap(dns)] or(More)
A reported mixed opioid agonist - neurokinin 1 receptor (NK1R) antagonist 4 (Dmt-D-Arg-Aba-Gly-(3',5'-(CF3)2)NMe-benzyl) was modified to identify important features in both pharmacophores. The new dual ligands were tested in vitro and subsequently two compounds (lead structure 4 and one of the new analogues 22, Dmt-D-Arg-Aba-β-Ala-NMe-Bn) were selected for(More)
There is strong evidence to indicate that a positively charged nitrogen of endogenous and exogenous opioid ligands forms a salt bridge with the Asp residue in the third transmembrane helix of opioid receptors. To further examine the role of this electrostatic interaction in opioid receptor binding and activation, we synthesized 'carba'-analogues of the(More)
The dermorphin-derived cyclic tetrapeptide analogues H-Tyr-c[D-Cys-Phe-Cys]NH(2) and H-Tyr-c[D-Cys-Phe-D-Cys]NH(2) are opioid agonists at the mu and delta receptor. To enhance the metabolic stability of these peptides, we replaced the disulfide bridge with a bis-methylene moiety. This was achieved by solid-phase synthesis of the linear precursor peptide(More)
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(More)
The cyclic enkephalin analog H-Tyr-D-Lys-Gly-Phe-Glu-NH2 (I) and the structurally related open chain analogs H-Tyr-D-Nle-Gly-Phe-Gln-NH2 (II) and H-Tyr-D-Lys(For)-Gly-Phe-Abu-NH2 (III) were tested in mu and delta opioid receptor-representative binding assays and bioassays. Whereas both linear analogs showed a pronounced preference for mu receptors over(More)
The side-chain to side-chain cyclized opioid peptide analogs H-Tyr-D-Orn-Phe-Asp-NH2 (I) and H-Tyr-D-Lys-Phe-Glu-NH2 (II) were synthesized and tested in the guinea pig ileum and mouse vas deferens assays and in binding assays based on displacement of mu- and delta-opioid receptor-selective radioligands from rat brain membranes. The more rigid cyclic analog(More)
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