Peter I. Dosa, PhD

Associate Program Director, Medicinal Chemistry, Institute for Therapeutics Discovery and Development (ITDD)

Peter I. Dosa

Contact Info

pidosa@umn.edu

Office Phone 612-625-7948

Fax 612-626-6318

Office Address:
717 Delaware Bldg, Room 457

Mailing Address:
University of Minnesota
Institute for Therapeutics Discovery & Development (ITDD)
717 Delaware Street SE
Minneapolis, Minnesota 55414

Associate Program Director, Medicinal Chemistry, Institute for Therapeutics Discovery and Development (ITDD)

Research Associate Professor, Department of Medicinal Chemistry

Research Associate Professor, Institute for Therapeutics Discovery and Development (ITDD)


PhD, University of California (Organic Chemistry)

MS, Massachusetts Institute of Technology (Chemistry)

AB, Princeton University (Chemistry - magna cum laude)

Summary

Research in the Dosa laboratory focuses on the discovery of new therapeutics, with a strong emphasis on modifying existing drugs or natural products to enhance their pharmacological or pharmacokinetic properties. Our research is highly collaborative and we work with investigators both internal and external to the University of Minnesota to help incorporate drug discovery into their research programs. Several of our most advanced research programs include: (I) The development of KATP channel openers as a new class of therapeutics to treat glaucoma; (II) The synthesis of gut-restricted bile acid analogs designed to inhibit C. difficile spore germination; and (III) GPCR-focused drug discovery.

I came to UMN in 2009 from Arena Pharmaceuticals, where I worked as a medicinal chemist in the drug discovery group on projects focusing on GPCRs. During the nearly seven years I was at Arena, I worked on several projects that reached the clinic including Arena’s 5-HT2C agonist program, which resulted in the approved drug lorcaserin.

Research

Research Summary/Interests

  • Drug Discovery
  • Prodrugs
  • GPCRs
  • Clostridium difficile
  • Serotonin and dopamine receptors

Publications

PubMed

1.Stoltz, K.S.; Erickson, R.; Staley, C.; Weingarden, A. R.; Romens, E.; Steer, C. J.; Khoruts, A.; Sadowsky, M. J.; Dosa, P. I.* Synthesis and biological evaluation of bile acid analogs inhibitory to Clostridium difficile spore germination. J. Med. Chem. 2017, Epub ahead of print.

2. Pollock, K.; Samsonraj, R. M.; Dudakovic, A.; Thaler, R.; Stumbras, A.; McKenna, D. H.; Dosa P. I.; van Wijnen, A. J.; Hubel, A. Improved post-thaw function and epigenetic changes in mesenchymal stromal cells cryopreserved using multicomponent osmolyte solutions. Stem Cells Dev. 2017, EPub ahead of print.

3. Roy Chowdhury, U.; Viker, K. B.; Stoltz, K. L.; Holman, B. H.; Fautsch, M. P.; Dosa, P. I.* Analogs of the ATP-sensitive potassium (KATP) channel opener cromakalim with in vivo ocular hypotensive activity. J. Med. Chem. 2016, 59, 6221-6231.

4. Pollock, K.; Yu, G.; Moller-Trane, R.; Koran, M.; Dosa, P. I.; McKenna, D. H.; Hubel, A. Combinations of osmolytes, including monosaccharides, disaccharides, and sugar alcohols act in concert during cryopreservation to improve mesenchymal stromal cell survival. Tissue Eng., Part C, 2016, 22, 999-1008.

5. Roy Chowdhury, U.; Dosa, P. I.; Fautsch, M. P. ATP sensitive potassium channel openers: a new class of ocular hypotensive agents. Exp. Eye Res. 2016, Epub ahead of print.

6. Pollock, K.; Budenske, J. W.; McKenna, D. H.; Dosa, P. I., Hubel, A. Algorithm-driven optimization of cryopreservation protocols for transfusion model cell types including Jurkats and mesenchymal stem cells. J. Tissue Eng. Regener. Med. 2016, Epub ahead of print.

7. Weingarden, A. R.; Dosa, P. I.; DeWinter, E.; Steer, C. J.; Shaughnessy, M. K.; Johnson, J. R.; Khoruts, A.; Sadowsky, M. J. Changes in colonic bile acid composition following fecal microbiota transplantation are sufficient to control Clostridium difficile germination and growth. PLoS ONE, 2016, 11, e0147210.

8. Dosa, P. I.*; Amin, E. A. Tactical approaches to interconverting GPCR agonists and antagonists, J. Med. Chem. 2016, 59, 810-840.

9. Weingarden, A. R.; Chen, C.; Zhang, N.; Graiziger, C. T.; Dosa, P. I.; Steer, C. J.; Shaughnessy, M. K.; Johnson, J. R.; Sadowsky, M. J.; Khoruts, A. Ursodeoxycholic acid inhibits Clostridium difficile spore germination and vegetative growth, and prevents the recurrence of ileal pouchitis associated with the infection. J. Clin. Gastroenterol., 2016, 50, 624-630.

10. Roy Chowdhury, U.; Bahler, C. K.; Holman, B. H.; Dosa, P. I.; Fautsch, M. P. Ocular hypotensive effects of the ATP-sensitive potassium channel opener cromakalim in human and murine experimental model systems. PLoS ONE, 2015, 10, e0141783.

11. Chan, J. D.; Agbedanu, P. N.; Grab, T.; Zamanian, M.; Dosa, P. I.; Day, T. A.; Marchant, J. S.  Ergot alkaloids (re)generate new leads as antiparasitics. PLoS Neglected Trop. Dis., 2015, 9, e0004063.

12. Dosa, P. I.; Georg, G. I.; Gurvich, V. J.; Hawkinson, J. E.; Walters, M. A.; Wong, H. L. From HTS to Phase I: The Institute for Therapeutics Discovery and Development at the University of Minnesota. Comb. Chem. High Throughput Screening, 2014, 17, 231-240.

13. Dosa, P. I.*; Ward, T.; Castro, R. E.; Rodrigues, C. M. P.; Steer, C. J. Synthesis and evaluation of water-soluble prodrugs of the anti-apoptotic bile acid UDCA. ChemMedChem, 2013, 8, 1002-1011.

14. Dosa, P. I.*; Ward, T.; Walters, M. A.; Kim, S. W. Synthesis of novel analogs of cabergoline: improving cardiovascular safety by removing 5-HT2B receptor agonism. ACS Med. Chem. Lett., 2013, 4, 254-258.

15. Xiong, Y.; Ullman, B.; Choi, K.; Cherrier, M.; Strah-Pleynet, S.; Decaire, M.; Dosa, P. I.; Feichtinger, K.; Teegarden, B. R.; Frazer, J. M.; Yoon, W. H.; Shan, Y.; Whelan, K.; Hauser, E. K.; Grottick, A. J.; Semple, G.; Al-Shamma, H. Synthesis and in vivo evaluation of phenethylpiperazine amides: selective 5-hydroxytryptamine2A receptor antagonists for the treatment of insomnia. J. Med. Chem., 2010, 53, 5696-5706.

16. Xiong, Y.; Teegarden, B. R.; Choi, K.; Strah-Pleynet, S.; Decaire, M.; Jayakumar, H.; Dosa, P. I.; Casper, M. D.; Pham, L.; Feichtinger, K.; Ullman, B.; Adams, J.; Yuskin, D.; Frazer, J.; Morgan, M.; Sadeque, A.; Chen, W.; Webb, R. R.; Connolly, D. T.; Semple, G.; Al-Shamma, H. Discovery and structure-activity relationship of 3-methoxy-N-(3-(1-methyl-1H-pyrazol-5-yl)-4-(2-morpholinoethoxy)phenyl)benzamide (APD791): a highly selective 5-hydroxytryptamine2A receptor inverse agonist for the treatment of arterial thrombosis. J. Med. Chem., 2010, 53, 4412-4421.

17. Teegarden, B. R.; Li, H.; Jayakumar, H.; Strah-Pleynet, S.; Dosa, P. I.; Selaya, S. D.; Kato, N.; Elwell, K. H.; Davidson, J.; Cheng, K.; Saldana, H.; Frazer, J. M.; Whelan, K.; Foster, J.; Espitia, S.; Webb, R. R.; Beeley, N.; Thomsen, W.; Morairty, S. R.; Kilduff, T. S.; Al-Shamma, H. Discovery of 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)-urea (Nelotanserin) and related 5-hydroxytryptamine2A inverse agonists for the treatment of insomnia. J. Med. Chem., 2010, 53, 1923-1936.

18. Dosa, P. I.*; Strah-Pleynet, S.; Jayakumar, H.; Casper, M.; Decaire, M.; Xiong, Y.; Lehmann, J.; Choi, K.; Elwell, K.; Wong, A.; Webb, R. R.; Adams, J. W.; Ramirez, J.; Richman, J. G.; Thomsen, W.; Semple, G.; Teegarden, B. R. Solubilized phenyl-pyrazole ureas as potent, selective 5-HT2A inverse-agonists and their application as antiplatelet agents. Bioorg. Med. Chem. Lett. 2009, 19, 5486-5489.

19. Albright, T. A.; Dosa, P. I.; Grossmann, T. N.; Khrustalev, V. N.; Oloba, O. A.; Padilla, R.; Paubelle, R.; Stanger, A.; Timofeeva, T. V.; Vollhardt, K. P. Photo-thermal haptotropism in cyclopentadienylcobalt complexes of linear phenylenes: intercyclobutadiene metal migration. Angew. Chem. Int. Ed. 2009, 48, 9853-9857.

20. Dosa, P. I.; Gu, Z.; Hager, D.; Karney, W. L.; Vollhardt, K. P. C. Flash-vacuum-pyrolytic reorganization of angular [4]phenylene. Chem. Comm. 2009, 15, 1967-1969.

21. Adams J.; Ramirez J.; Ortuno D.; Shi Y.; Thomsen W.; Richman J.; Morgan M.; Dosa P.; Teegarden B.; Al-Shamma H.; Behan D.; Connolly D. Anti-thrombotic and vascular effects of AR246686, a novel 5-HT2A receptor antagonist. Eur. J. Pharmacol. 2008, 586, 234-43.

22. Smith, B.; Smith, J.; Tsai, J.; Schultz, J.; Gilson, C.; Estrada, S.; Chen, R.; Park, D.; Prieto, E.; Gallardo, C.; Sengupta, D.; Dosa, P.; Covel, J.; Ren, A.; Webb, R.; Beeley, N.; Martin, M.; Morgan, M.; Espitia, S.; Saldana, H.; Bjenning, C.; Whelan, K.; Grottick, A.; Menzaghi, F.; Thomsen, W. Discovery and structure-activity relationship of (1R)-8-chloro-2,3,4,5-tetrahydro-1-methyl-1H-3-benzazepine (Lorcaserin), a selective serotonin 5-HT2C receptor agonist for the treatment of obesity. J. Med. Chem. 2008, 51, 305-313.

23. Bong, D.; Chan, E. W. L.; Diercks, R.; Dosa, P. I.; Haley, M. M.; Matzger, A. J.; Miljanic, O. S.; Vollhardt, K. P. C.; Bond, A. D.; Teat, S. J.; Stanger, A. Synthesis of syn and anti doublebent [5]phenylene. Org. Lett. 2004, 6, 2249-2252.

24. Dosche, C.; Kumke, M. U.; Ariese, F.; Bader, A. N.; Gooijer, C.; Dosa, P. I.; Han, S.; Miljanic, O. S.; Vollhardt, K. P. C.; Puchta, R.; van Eikema Hommes, N. J. R. Shpol’skii spectroscopy and vibrational analysis of [N]phenylenes. Phys. Chem. Chem. Phys. 2003, 5, 4563-4569.

25. Dosche, C. Loehmannsroeben, H.-G.; Bieser, A.; Dosa, P. I.; Han, S.; Iwamoto, M.; Schleifenbaum, A.; Vollhardt, K. P. C. Photophysical properties of [N]phenylenes. Phys. Chem. Chem. Phys. 2002, 4, 2156-2161.

26. Dosa, P. I.; Whitener, G. D.; Vollhardt, K. P. C.; Bond, A. D.; Teat, S. J. Cobalt-mediated synthesis of angular [4]phenylene: structural characterization of a metallacyclopentadiene(alkyne) intermediate and its thermal and photochemical conversion. Org. Lett. 2002, 4, 2075-2078.

27. Dosa, P. I.; Schleifenbaum, A.; Vollhardt, K. P. C. Isomerization of linear to angular [3]phenylene and PAHs under flash vacuum pyrolysis conditions. Org. Lett. 2001, 3, 1017-1020.

28. Dosa, P. I.; Erben, C.; Iyer, V. S.; Vollhardt, K. P. C.; Wasser, I. M. Metal encapsulating carbon nanostructures from oligoalkyne metal complexes. J. Am. Chem. Soc. 1999, 121, 10430-10431.

29. Dosa, P. I.; Fu, G. C. Catalytic asymmetric addition of ZnPh2 to ketones: enantioselective formation of quaternary stereocenters. J. Am. Chem. Soc. 1998, 120, 445-446.

30. Dosa, P. I.; Ruble, J. C.; Fu, G. C. Planar-chiral heterocycles as ligands in metal-catalyzed processes: enantioselective addition of organozinc reagents to aldehydes. J. Org. Chem. 1997, 62, 444-445.

31. Dosa, P.; Kronish, I.; McCallum, J.; Schwartz, J.; Barden, M. C. Titanium complex-catalyzed borohydride reduction of azobenzenes. J. Org. Chem. 1996, 61, 4886-4887.