My research is concerned with the design, synthesis, and biological evaluation of ligands for their use as tools and potential analgesic agents at opioid receptors. We are particularly interested in mechanisms for the association of such ligands with opioid receptors. Of particular interest is the role of heteromerization of GPCRs in signaling.
(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
Goudie-DeAngelis EM, Abdelhamid RE, Nunez MG, Kissel CL, Kovács KJ, Portoghese PS, Larson AA. Modulation of musculoskeletal hyperalgesia by brown adipose tissue activity in mice. Pain. 2016 Jul 19;.
Akgün E, Javed MI, Lunzer MM, Powers MD, Sham YY, Watanabe Y, Portoghese PS. Inhibition of Inflammatory and Neuropathic Pain by Targeting a Mu Opioid Receptor/Chemokine Receptor5 Heteromer (MOR-CCR5). J. Med. Chem. 58, 8647-8657 (2015).
Smeester BA, Lunzer MM, Akgün E, Beitz AJ, Portoghese PS. Targeting putative mu opioid/metabotropic glutamate receptor-5 heteromers produces potent antinociception in a chronic murine bone cancer model. Eur J Pharmacol. 2014 Nov 15;743:48-52.
Le Naour M, Lunzer MM, Powers MD, Kalyuzhny AE, Benneyworth MA, Thomas MJ, Portoghese PS. Putative kappa opioid heteromers as targets for developing analgesics free of adverse effects. J Med Chem. 2014 Aug 14;57(15):6383-92.
Akgün E, Javed MI, Lunzer MM, Smeester BA, Beitz AJ, Portoghese PS. Ligands that interact with putative MOR-mGluR5 heteromer in mice with inflammatory pain produce potent antinociception. Proc Natl Acad Sci U S A. 2013 Jul 9;110(28):11595-9.
Pravetoni M, Le Naour M, Harmon T, Tucker A, Portoghese PS, Pentel PR. An oxycodone conjugate vaccine elicits oxycodone-specific antibodies that reduce oxycodone distribution to brain and hot-plate analgesia. J Pharmacol Exp Ther. 2012 Jan 18.
Le Naour M, Lunzer MM, Powers MD, Portoghese PS. Opioid Activity of Spinally Selective Analogues of N-Naphthoyl-β-naltrexamine in HEK-293 Cells and Mice. J Med Chem. 2012 Jan 5.
Yekkirala AS, Lunzer MM, McCurdy CR, Powers MD, Kalyuzhny AE, Roerig SC, Portoghese PS. N-naphthoyl-beta-naltrexamine (NNTA), a highly selective and potent activator of μ/kappa-opioid heteromers. Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):5098-103. Epub 2011 Mar 8.
Yekkirala, A.S.; Kalyuzhny, A.E.; Portoghese, P.S. Standard opioid agonists activate heteromeric opioid receptors: evidence for morphine and [D-Ala2,MePhe4Glyol5]enkkephalin as selective agonists. ACS Chem. Neurosci. 1, 146-154 (2010).
Harikumar, K.G.; Akgun, E.; Portoghese, P.S.; Miller, L.J. Modulation of cell surface non-activated cholecystokinin receptors using bivalent ligand-induced internalization. J. Med. Chem. 53, 2836-2842 (2010).
Ansinoff, M.A.; Portoghese, P.S.; Pintar, J.E. Consequences of opioid receptor mutation on actions of univalent and bivalent kappa and delta ligands. Psychopharmacol. 210, 161-168 (2010)