Eyup Akgun, MS, PhD

Research Associate Professor, Department of Medicinal Chemistry

Eyup Akgun

Contact Info

akgun001@umn.edu

Office Phone 612-624-1988

Office Address:
8-106 Weaver-Densford Hall

Research Associate Professor, Department of Medicinal Chemistry


PhD of Medicinal Chemistry, University of Marburg

Master of Organic Chemistry, University of Marburg

Bachelor of Chemistry, University of Marburg

Summary

Our laboratory targets chemokine-mGluR5 heteromer for treatment of neurodegenerative diseases. Neurodegenerative diseases affect a significant segment of the world’s population. A common feature associated with this group of diseases is chronic neuronal inflammation. Chemokines via their receptors play major role in this process by contributing to inflammation through increased glutamate release from astrocytes. Chronic high levels of glutamate create neurotoxicity by persistent stimulation of metabotropic glutamate-5 (mGluR5) and ionotropic (NMDA) receptors on neurons which lead to degeneration. The chemokine receptors and mGluR5 are co localized in glia as well as in neurons. Studies suggest functional cross-talk between chemokinereceptors and mGluR5 that mediates neuro-immune processes that play important roles in neuro-immuno communication. These heteromer may play an important role in neurodegeneration processes in the CNS. We develop bivalent ligands that contain antagonist phamacophores for chemokines (CCR5, CXCR4) etc. and mGluR5 for halting the progression of neurodegenerative diseases such as multiple sclerosis, Alzheimer’s, and neuroAIDS-associated dementia. The bivalent ligands are evaluated in vitro as well as in vivo using animal models.

Awards & Recognition

  • Award for Cancer Research- 1990 (Wesley Foundation, Kansas)
  • Scientist of the year- 1987 (Sedat Simavi Foundation, Turkey)
  • Scholarship for Successful Foreign Student- 1972 (West Germany)

Research

Publications

PubMed

  • A bivalent ligand that activates mu opioid receptor and antagonizes mGluR5 receptor reduces neuropathic pain in mice.Peterson CD1, Kitto KF, Akgün E, Lunzer MM, Riedl MS, Vulchanova L, Wilcox GL, Portoghese PS, Fairbanks CA.Pain. 2017 Sep 1. doi: 10.1097/j.pain.0000000000001050. [Epub ahead of print]
    Heteromer induction: An approach to unique pharmacology? Portoghese, P.S.; Akgün, E.; Lunzer, M. ACS Chemical Neuroscience 2017, 318, 426-428.
    Inhibition of Inflammatory and Neuropathic Pain by Targeting a Mu Opioid Receptor/Chemokine Receptor5 Heteromer (MOR-CCR5). Akgün, E.; Javed, M. I.; Lunzer, M. M.; Powers, M. D.; Sham, Y. Y.; Watanabe, Y.; Portoghese, P. S. J. Med. Chem. 2015, 58, 8647-8657.
  • Targeting putative mu opioid/metabotropic glutamate receptor-5 heteromers produces potent antinociception in a chronic murine bone cancer model. B. A. Smeester, M. M. Lunzer, E. Akgün, A. J. Beitz, P. S. Portoghese. Eur. J. Pharmacol. 2014, 743, 48-52.
  • Ligands that interact with putative MOR-mGluR5 heteromer in mice with inflammatory pain produce potent antinociception. Akgün, E.; Javed, M.I.; Lunzer, M.M.; Smeester, B.A.; Beitz, A.B.;. Portoghese. P.S. Proceedings of the National Academy of Sciences 2013, 110, 11595-11599
  • Bivalent Ligands That target mu Opioid (MOP) and Cannabinoid1 (CB1) Receptors Are Potent Analgesics Devoid of Tolerance. Le Naour, M.; Akgün, E.; Yekkirala, A.; Lunzer, M.M.; Powers, M. D.; Kalyuzhny, A.E.; Portoghese, P.S. J. Med. Chem. 2013, 56, 5505-5513.
  • Molecular Basis for Binding and Subtype Selectivity of 1, 4-Benzodiazepine ntagonist Ligands of the Cholecystokinin Receptor. Cawston, E. E.; Lam, P.C. H.; Harikumar, K. G.; Dong, M.; Ball, A. M.;. Augustine, M. L.; Akgün, E.; Portoghese, P. S.; Orry, A.; Abagyan, R.; Sexton, P. M. and Miller, L. J. J.Biol.Chem. 2012, 287(22), 18618–18635.
  • MDAN-21: A Bivalent Opioid Ligand Containing Mu-Agonist and Delta-Antagonist Pharmacophores and Its Effects in Rhesus Monkeys. Aceto, M. D.; Harris, L. S.; Negus, S. S.; Banks, M. L.; Hughes, L. D.; Akgün, E. and Portoghese, P. S. Int.J.Med.Chem. 10.1155/2012/327257.
  • Modulation of Cell Surface Expression of Nonactivated Cholecystokinin Receptors Using Bivalent Ligand-Induced Internalization. Harikumar, K.G.; Akgün, E.;. Portoghese, P.S.; Miller, L.J. J.Med.Chem. 2010, 53: 2836-2842.
  • Modulation of Cell Surface Expression of Nonactivated Cholecystokinin Receptors Using Bivalent Ligand-Induced Internalization. Harikumar, K.G.; Akgün, E.; Portoghese, P.S.;Miller, L.J J. Med. Chem. 2010, 53: 2836-2842.
  • Synthesis and in Vitro Characterization of Radioiodinatable Benzodiazepines Selective for Type 1 and Type 2 Cholecystokinin Receptors. Akgün, E.; Körner, M.;Gao, F. Harikumar, K.G.; Waser, B.; Reubi, J.C.; J.; Portoghese, P.S.;Miller, L.J. J. Med. Chem. 2009, 52(7):2138-2147.
  • A Bivalent ligand (MDAN-21) containing µ-agonist and ?- antagonist pharmacophores is devoid of significance physical dependence capacity in rats. Aceto, M.D., Portoghese, P.S., Akgün, E., Harris, L.S. cpdd 2009, June 20-25, Reno/Sparks, Nevada Control.ID: 586278.
  • Induction of heterodimerization of mu opioid (MOP) and type B cholecystokinin (CCKB) receptors by bivalent ligands.
  • Zheng, Y.; Akgün, E.; Harikumar, K.G.; Hopson, Powers, M. D., Lunzer, M.M., J.; Miller, L.J.; Portoghese, P.S. J.Med.Chem. 2009, 52 (2), pp 247–258.
  • Induction of heterodimerization of mu opioid peptide (MOP) and type-2 cholecystokinin (CCK2) receptor by novel bivalent ligands. Eyup Akgün, Yaguo Zheng, Kaleeckal G. Harikumar, Jessika Hopson, Laurence J. Miller, Philip S. Portoghese. Drugs Fut 2008, 33(Suppl. A): XXth Int Symp Med Chem (Aug31-Sept4, Vienna) 2008.