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Philip Portoghese, Ph.D. Professor, Department of Medicinal Chemistry E-mail: porto001@umn.edu

Research Interests:

My interests are focused on the design and synthesis of ligands as probes to investigate opioid 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. The design of selective opioid receptor antagonists and affinity labels has been a key area of interest. These studies have employed site-directed mutogenesis as an aid in an effort to obtain insight into the recognition of ligands by opioid receptors. Our most recent studies involve ligands that selectively target heterodimers containing opioid receptors.

Selected Publications:

Haris SP, Zhang Y, Le Bourdonnec B, McCurdy CR, Portoghese PS. o-Naphthalenedicarboxaldehyde derivative of 7'-aminonaltrindole as a selective delta-opioid receptor affinity label. J Med Chem. 2007 Jul 12;50(14):3392-6.

Lenard NR, Daniels DJ, Portoghese PS, Roerig SC. Absence of conditioned place preference or reinstatement with bivalent ligands containing mu-opioid receptor agonist and delta-opioid receptor antagonist pharmacophores. Eur J Pharmacol. 2007 Jul 2;566(1-3):75-82.

Lunzer MM, Portoghese PS. Selectivity of delta- and kappa-opioid ligands depends on the route of central administration in mice. J Pharmacol Exp Ther. 2007 Jul;322(1):166-71.

Lunzer MM, Yekkirala A, Hebbel RP, Portoghese PS. Naloxone acts as a potent analgesic in transgenic mouse models of sickle cell anemia. Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):6061-5.

Daniels DJ, Lenard NR, Etienne CL, Law PY, Roerig SC, Portoghese PS. Opioid-induced tolerance and dependence in mice is modulated by the distance between pharmacophores in a bivalent ligand series. Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):19208-13.

Xie Z, Bhushan RG, Daniels DJ, Portoghese PS. Interaction of bivalent ligand KDN21 with heterodimeric delta-kappa opioid receptors in human embryonic kidney 293 cells. Mol Pharmacol. 2005 Oct;68(4):1079-86.

Waldhoer M, Fong J, Jones RM, Lunzer MM, Sharma SK, Kostenis E, Portoghese PS, Whistler JL. A heterodimer-selective agonist shows in vivo relevance of G protein-coupled receptor dimers. Proc Natl Acad Sci U S A. 2005 Jun 21;102(25):9050-5.

Zhang Y, Sham YY, Rajamani R, Gao J, Portoghese PS. Homology modeling and molecular dynamics simulations of the mu opioid receptor in a membrane-aqueous system. Chembiochem. 2005 May;6(5):853-9.

Daniels DJ, Kulkarni A, Xie Z, Bhushan RG, Portoghese PS. A bivalent ligand (KDAN-18) containing delta-antagonist and kappa-agonist pharmacophores bridges delta2 and kappa1 opioid receptor phenotypes. J Med Chem. 2005 Mar 24;48(6):1713-6.

Zhang Y, McCurdy CR, Metzger TG, Portoghese PS. Specific cross-linking of Lys233 and Cys235 in the mu opioid receptor by a reporter affinity label. Biochemistry. 2005 Feb 22;44(7):2271-5.