Thrombostatin Fm19 ‐ A Thrombin Receptor Activation Antagonist

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106110/1/jth01272.pd

Pharmacophore elements of the TIPP class of delta opioid receptor antagonists

A series of tri-and tetrapeptides sharing the amino-terminal dipeptide unit Tyr-Tic, found in the high-affinity delta opioid receptor antagonist Tyr-Tic-Phe-Phe (TIPP), was prepared and evaluated in receptor binding assays to explore the role(s) of the phenylalanine residues in positions 3 and 4. It was found that aromaticity of residues 3 and 4 is not required for high affinity, a lipophilic side chain in either location being sufficient, as evidenced by the high delta receptor binding affinities observed for the tetrapeptide Tyr-Tic-Ala-Leu and the tripeptide Tyr-Tic-Leu. These results support the suggestion of Temussi et al. [Biochem. Biophys. Res. Commun., 198 (1994) 933] that the aromatic side chain of the Tic residue corresponds to the aromatic side chain found in residues 3 or 4 in other delta-selective peptide series.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43172/1/10989_2004_Article_BF00126275.pd

Modifications of the cyclic mu receptor selective tetrapeptide Tyr-c[d-Cys-Phe-d-Pen]NH 2 (Et): effects on opioid receptor binding and activation

The previously described cyclic mu opioid receptor-selective tetrapeptide Tyr-c[d-Cys-Phe-d-Pen]NH 2 (Et) (JOM-6) was modified at residues 1 and 3 by substitution with various natural and synthetic amino acids, and/or by alteration of the cyclic system. Effects on mu and delta opioid receptor binding affinities, and on potencies and efficacies as measured by the [ 35 S]-GTPγS assay, were evaluated. Affinities at mu and delta receptors were not influenced dramatically by substitution of Tyr 1 with conformationally restricted phenolic amino acids. In the [ 35 S]-GTPγS assay, all of the peptides tested exhibited a maximal response comparable with that of fentanyl at the mu opioid receptor, and all showed high potency, in the range0.4–9 nm. However, potency changes did not always correlate with affinity, suggesting that the conformation required for binding and the conformation required for activation of the opioid receptors are different. At the delta opioid receptor, none of the peptides were able to produce a response equivalent to that of the full delta agonist BW 373,U86 and only one had an EC 50 value of less than 100 nm. Lastly, we have identified a peptide, d-Hat-c[d-Cys-Phe-d-Pen]NH 2 (Et), with high potency and > 1000-fold functional selectivity for the mu over delta opioid receptor as measured by the [ 35 S]-GTPγS assay.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71802/1/j.1399-3011.2000.00177.x.pd

Design of high affinity cyclic pentapeptide ligands for kappa-opioid receptors

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73319/1/j.1399-3011.2005.00295.x.pd