Education:

B.S., Columbia University, 1953
Ph.D., University of Wisconsin, 1961

Research Interests:

My interests are focused on the design and synthesis of ligands as probes to investigate pharmacologic receptors. One of the main objectives of my research is to develop new approaches and concepts to designing highly selective ligands. Most of my recent research has been involved with the design and synthesis of ligands that are selective for different opioid receptor types. These studies have utilized both animal studies and cloned receptors as an aid to obtain insight into the recognition of ligands by opioid receptors.

Publications:

“A bivalent ligand (KDAN-18) containing delta-antagonist and kappa-agonist pharmacophores bridges gamma2 and kappa1 opioid receptor phenotypes.”  D.J. Daniels, A. Kulkarni, Z. Xie, R.G. Bhushan, P.S. Portoghese, J. Med. Chem. 48, 1713-1716, (2005).

"A Heterodimer-Selective Agonist Shows in Vivo Relevance of G Protein-Coupled Receptor Dimers". Waldhoer, M.; Fong, J.; Jones, R. M; Lunzer, M. M.; Sharma, S. K.; Kostenis, E.; Portoghese, P. S.; Whistler, J. L.;  Proc. Natl. Acad. Sci. U.S.A. 102, 9050-9055,(2005).

“Specific cross-linking of Lys233 and Cys235 in the mu opioid receptor by a reporter affinity label.”  Y. Zhang, C.R. McCurdy, T.G. Metzger, P.S. Portoghese, Biochem. 44, 2271-2275, (2005).

“Comparison of peptidic and nonpeptidic delta-opioid agonists on guanosine 5’-O-(3-[35S]thio)triphosphate ([35S]GTP gamma S) binding in brain slices from sprague-dawley rats.”  E.M. Jutkiewicz, N.P. Walker, J.E. Folk, K.C. Rice, P.S. Portoghese, J.H. Woods, J.R. Traynor, J. Pharmaacol. and Exp. Ther. 312, 1314-1320, (2005).

“Homology modeling and molecular dynamics simulations of the mu opioid receptor in a menbrane-aqueous system,” Y. Zhang, Y. Sham, R. Rajamani, J. Gao, and P.S. Portoghese, ChemBioChem, 6, 1-7 (2005).

“A Bivalent Ligand (KDN-21) Reveals Spinal δ and κ Opioid Receptors are Organized as Heterodimers that Give Rise to δ;1 and κ;2 Phenotypes. Selective targeting of δ; κ; Heterodimers.” R.G. Bhushan, S.K. Shiv, Z. Xie, D.J. Daniels, and P.S. Portoghese, Journal of Medicinal Chemistry, 47(12), 2969-2972 (2004).

“Delta-Selective Ligands Related to Naltrindole.” D.J. Daniels and P.S. Portoghese, in The Delta Receptor; K.-J. Chang, F. Porreca, and J.H Woods, Eds., Marcel Dekker, Inc., New York, 2004, pp 139-158.

"Characterization of Specific Opioid Binding Sites in Neural Membranes from the Myenteric Plexus of Porcine Small Intestine." D.Townsend IV, P. S. Portoghese, and D. R. Brown, J. Pharmacol. Exp. Ther., 308, 385-393 (2004).

"Antidepressant-like effects of kappa-opioid receptor antagonists in the forced swim test in rats." S.D. Mague, A.M. Pliakas, M.S. Todtenkopf, H.C. Tomasiewicz, Y. Zhang, W.C. Stevens,  Jr., R.M. Jones, P.S. Portoghese, and W.A. Carlezon, Jr., J. Pharmacol. Exp. Ther., 305, 323-330 (2003).

 "Effect of opioid receptor ligands on the mu-S196A knock-in and mu knockout mouse vas deferens. P.S. Portoghese," P.-Y. Law, H.H. Loh, Eur. J. Pharmacol. 478, 207-210 (2003).

Identity of the putative delta-1 opioid receptor as a delta-kappa heteromer in the mouse spinal cord.  Portoghese, P. S.; Lunzer, M. M.  Eur. J. Pharmacol. 467, 233-234 (2003).

Antidepressant-like effects of kappa-opioid receptor antagonists in the forced swim test in rats. Mague, S. D.; Pliakas, A. M.; Todtenkopf, M. S.; Tomasiewicz, H. C.; Zhang, Y.; Stevens, W. C., Jr.; Jones, R. M.; Portoghese, P. S.; Carlezon, W. A., Jr.  J. Pharmacol. Exp. Ther., 305,  323-330 (2003).

Naphthalene dicarboxaldehyde as an electrophilic fluorogenic moeity for affinity labeling.  Application to opioid receptor affinity labels with greatly improved fluorogenic properties, C.R. McCurdy, B. LeBourdonnec, T.G. Metzger, R. El Kouhen, Y. Zhang, P.Y. Law, and P.S. Portoghese, J. Med Chem. 45, 2887-2890 (2002).

Kappa opioid antagonist effects of the novel kappa antagonist 5'-guanidinonaltrindole (GNTI) in an assay of schedule-controlled behavior in rhesus monkeys.  S. S. Negus, N.K. Mello, D.C. Linsenmayer, R.M. Jones, P.S. Portoghese.  Psychopharmacol, 163(3-4), 412-419 (2002).