Education

• Ph.D. in Organic Chemistry - Summa Cum Laude from University of Veszprem, Veszprem, Hungary.
• M.Sc. in Chemistry - Summa Cum Laude from University of Veszprem, Veszprem, Hungary.
• B.Sc. in Chemical Engineering –Summa Cum Laude from University of Veszprem, Veszprem, Hungary.

Profile

Dr. Prokai-Tatrai is a Professor of Pharmaceutical Sciences at UNT System College of Pharmacy at Fort Worth, TX where she is an award winning researcher and pharmacy educator. Her primary research interest has been on innovative and multidisciplinary projects focusing on medicinal chemistry-driven drug design and delivery into the central nervous system. Her projects integrates medicinal chemistry, biopharmaceutics, pharmacokinetics, metabolism and drug distribution studies in early-phase drug discovery and the development of neuroactive/neuroprotective agents. She has extensively published in a broad field of medicinal and pharmaceutical chemistry. A best testimony of a very recent success of her lab has been published in Science Translational Medicine. This seminal paper describes the very first brain-selective delivery of estrogens based on a unique bioprecursor prodrug approach. She has six issued US patents and has been an editorial board member of numerous journals and an academic editor of a successful special issue on neuroprotection.

Research Interest

• Medicinal and pharmaceutical chemistry with special emphasis on drug design and non-invasive drug delivery into the central nervous system.
• Neuroprotective strategies with special emphasis on the aging and injured brain.
• Neuropeptides as lead compounds for central nervous system drug design.
• Combinatorial lead optimization.
• NMR-based structure elucidation.
• Phenolic antioxidants with special emphasis on estrogens.
• Mass spectrometry–based proteomics with special emphasis on protein carbonylation and nitration.
• Chromatography-coupled mass spectrometry-based bioanalytical analyses.

Professional Activities:

Honors and Awards

Publications

Book Edited

• Prokai, L., Prokai-Tatrai, K. Peptide transport and delivery into the central nervous system, Progress in Drug Research Series, Vol. 61, Birkhäuser, Basel, 2003, pp. 245.

Book Chapters

• Prokai-Tatrai, K., Prokai, L. “Prodrug design for brain delivery of small-and medium-sized neuropeptides,” in Neuropeptides: Methods and Protocols (A. Merighi, Ed.), “Methods in Molecular Biology” Vol. 789, Series, Humana, Totowa, NJ, 2011, 313-336.
•  Prokai-Tatrai, K., Prokai, L. “The impact of metabolism on the safety of estrogen therapy,” in Annals of the New York Academy of Sciences (M. Singh, Ed.), NY Acad. of Sci., New York, NY, 2005, 243-247.
• Prokai-Tatrai, K., Prokai, L. “Modifying peptide properties by prodrug design for enhanced transport into the CNS,” in Progress in Drug Research, Vol. 61 (L. Prokai and K. Prokai-Tatrai, Eds.), Birkhäuser, Basel, 2003, 155-188.
• Prokai, L., Prokai-Tatrai, K., “Prodrugs,” in Pain, Irritation and Muscle Damage with Injectable Products (P. Gupta and G. Brazeau, Eds.), Interpharm Press, Buffalo Grove, IL, 1999, 267-306.
• Prokai, L., Prokai-Tatrai, K., Wu, W.-M., Wu, J., Ouyang, X., Kim, H.-S., Zharikova, A., Simpkins, J., Bodor, N. "Brain delivery and targeting of thyrotropin-releasing hormone analogs by covalent packaging and sequential metabolism," in Peptides: Chemistry, Structure and Biology (J.P. Tam and P.T.P. Kaumaya, Eds.), Kluver Academic, Dordrecht, The Netherlands, 1998, 834-836.

Peer Reviewed Papers

• Prokai, L., Nguyen, V., Szarka, S., Garg, P., Sabnis, G., Bimonte-Nelson, H.A., McLaughlin, K.J., Talboom, J.S., Conrad, C.D., Shughrue, P.J., Gould, T.D., Brodie, A., Merchenthaler, I., Koulen, P., Prokai-Tatrai, K. “The bioprecursor prodrug 10β,17β-dihydroxyestra-1,4-dien-3-one delivers 17β-estradiol selectively to the female brain,” Science Translational Medicine 7(297):297ra113 (2015).
• Szarka, S., Prokai-Tatrai, K., Prokai L. “Application of screening experimental designs for assessing chromatographic isotope effect through isotope-coded derivatization,” Analytical Chemistry 86, 7033-7040 (2014).
• Prokai, L., Guo, J., Prokai-Tatrai, K. “Selective chemoprecipitation of nitropeptides from complex proteomes for mass spectrometric analysis,” Nature Protocols 9, 882–895 (2014).
• Prokai-Tatrai, K., Xin, H., Nguyen. V., Szarka. S., Blazics, B., Prokai. L., Koulen, P. “17β-Estradiol eye drops protect the retinal ganglion cell layer and preserve visual function in an in vivo model of glaucoma,“ Molecular Pharmaceutics 10, 3253-3261 (2013).
• Prokai-Tatrai, K., Nguyen, V., Szarka, S., Konya, K., Prokai, L. “Design and exploratory neuropharmacological evaluation of novel thyrotropin-releasing hormone analogs and their brain-targeting bioprecursor prodrugs,” Pharmaceutics 5, 318-328 (2013).
• Prokai, L., Rivera-Portalatin, N.M., Prokai-Tatrai, K. “Quantitative structure–activity relationships predicting the antioxidant potency of 17β-estradiol-related polycyclic phenols to inhibit lipid peroxidation,” International Journal of Molecular Sciences 14, 1443-1454 (2013).
• Prokai-Tatrai, K., Nguyen, V., Szarka, S., Sahyouni, F., Walker, C., White, S., Talamantes, T., Prokai, L. ““All in the mind”? Brain-targeting chemical delivery system of 17β-estradiol produces significant yet undesirable uterotrophic side-effect,” Pharmaceutical Analytical Acta S7-002 (2013).
• Szarka, S., Prokai, L., Prokai-Tatrai, K. “Separation of dansylated 17β-estradiol, 17α-estradiol and estrone on a single HPLC column for simultaneous quantitation by LC-MS/MS,“ Analytical & Bioanalytical Chemistry 405, 3399-3406 (2013).
• Guo, J., K. Prokai-Tatrai, Prokai, L. “Relative quantitation of protein nitration by liquid chromatography–mass spectrometry using isotope-coded dimethyl labeling and chemoprecipitation,” Journal of Chromatography A 1232, 266–275 (2012).
• Prokai, L., Szarka, S., Wang, X., Prokai-Tatrai, K. “Capture of the volatile carbonyl metabolite of flecainide on 2,4-dinitrophenylhydrazine cartridge for quantitation by stable-isotope dilution mass spectrometry coupled with chromatography,” Journal of Chromatography A 1232, 281-287 (2012).
• Guo, J., K. Prokai-Tatrai, Ngyuen, V., Rauniyar, N., Ughy, B., Prokai, L. “Protein targets for carbonylation by 4-hydroxy-2-nonenal in rat liver mitochondria,” Journal of Proteomics 74, 2370-2379 (2011).
• Prokai-Tatrai, K., Guo, J., Prokai, L. “Selective chemoprecipitation and subsequent release of tagged species for the analysis of nitropeptides by liquid chromatography–tandem mass spectrometry,” Molecular & Cellular Proteomics 10, 10.1074/mcp.M110.002923, 1-10 (2011).
• Nguyen, V., Zharikova, A.D., Prokai-Tatrai, K., Prokai, L. “[Glu2]TRH dose-dependently attenuates TRH-evoked analeptic effect in the mouse brain,” Brain Research Bulletin 82, 83-86 (2010).
• Rauniyar, S.M., Prokai-Tatrai, K., Prokai, L. “Identification of carbonylation sites in apomyoglobin after exposure to 4-hydroxy-2-nonenal by solid-phase enrichment and liquid chromatography–electrospray ionization tandem mass spectrometry,” Journal of Mass Spectrometry 45, 398-410 (2010).
• Prokai-Tatrai, K., Bonds, D., Prokai, L. “Simultaneous measurement of 17β-estradiol, 17α-estradiol and estrone by GC–isotope dilution MS/MS,” Chromatographia 71, 311-315 (2010).
• Prokai-Tatrai, K., Prokai, L., Simpkins, J.W., Jung, M.E. “Phenolic compounds protect cultured hippocampal neurons against ethanol-withdrawal induced oxidative stress,” International Journal of Molecular Sciences 10, 1773-87 (2009).
• Prokai-Tatrai, K., Prokai, L. “Prodrugs of thyrotropin-releasing hormone and related peptides as central nervous system agents,” Molecules 14, 2633-654 (2009).
• Rauniyar, S.M., Stevens Jr. SM., Prokai-Tatrai, K., Prokai, L. “Characterization of 4-hydroxy-2-nonenal-modified peptides by liquid chromatography–tandem mass spectrometry using data-dependent acquisition: neutral loss-driven MS3 versus neutral loss-driven electron capture dissociation,” Analytical Chemistry 81, 782-789 (2008).
• Prokai-Tatrai, K., Kim, HS., Prokai, L. “The utility of oligopeptidase in brain-targeting delivery of an enkephalin analogue by prodrug design,” Open Medicinal Chemistry 2, 97-100 (2008).
• Stevens Jr., SM., Prokai-Tatrai, K., Prokai, L. “Factors that contribute to the misidentification of tyrosine nitration by shotgun proteomics,” Molecular & Cellular Proteomics 7, 2442-2455 (2008).
• Prokai-Tatrai, K., Perjesi, P., Rivera-Portalatin, N., Simpkins, J.W., Prokai, L. “Mechanistic investigations on the antioxidant action of a neuroprotective estrogen derivative,” Steroids 73, 280-288 (2008).
• Rivera-Portalatin, N., Serrano-Vera, J.L., Prokai-Tatrai, K., Prokai, L. “A crucial difference between estrogen-derived ortho-quinones and para-quinols regarding induction of oxidative stress,” The Journal of Steroid Biochemistry and Molecular Biology 105, 71-75 (2007).
• Prokai-Tatrai, K., Rivera-Portalatin, N., Rauniyar, N., Prokai, L. “A facile microwave-assisted synthesis of p-quinols by lead(IV) acetate oxidation,” Letters in Organic Chemistry 4, 265-267 (2007).
• Teixido, M., Prokai-Tatrai, K., Wang, X., Nguyen, V., Prokai, L. “Exploratory neuropharmacological evaluation of a bridged thyrotropin-releasing hormone analogue,” Brain Research Bulletin 73, 103-107 (2007).
• Prokai, L., Zharikova, A.D., Juhasz, A., Prokai-Tatrai, K. “Cardiovascular effects of neuropeptide FF antagonists,” Peptides 27, 1015-1019 (2006).
• Prokai, L., Prokai-Tatrai, K., Perjesi, P., Simpkins, J.W. “Mechanistic insights into the direct antioxidant effects of estrogens,” Drug Development Research 66, 118-125 (2006).
• Stevens, S.M. Jr., Prokai-Tatrai, K., Prokai, L. “Screening of combinatorial libraries for substrate preference by mass spectrometry,” Analytical Chemistry 77, 698-701 (2005).
• Prokai-Tatrai, K., Teixido, M., Nguyen, V., Zharikova, A.D., Prokai, L. “A pyridinium-substituted analogue of the TRH-like tripeptide pGlu-Glu-Pro-NH2 and its prodrugs as central nervous system agents,” Medicinal Chemistry 1, 141-152 (2005).
• Prokai, L., Prokai‐Tatrai, K., Pop, E., Bodor, N., Lango, J., Roboz, J. “Fast atom bombardment and tandem mass spectrometry of quaternary pyridinium salt‐type tryptophan derivatives”, Journal of Mass Spectrometry 28, 707 – 715 (2005).
• Prokai, L., Prokai-Tatrai, K., Perjesi, P., Zharikova, A.D., Perez, EJ., Gleason, K. Simpkins, J.W. ”Hydoxyl-radical scavenging mechanism of a neuroprotective estrogen derivative,“ Free Radical Biology and Medicine 37, S40-S41(2004).
• Prokai, L., Prokai-Tatrai, K., Zharikova, A.D., Nguyen, V., Perjesi, P., Stevens, S.M. Jr. “Centrally-acting and metabolically stable thyrotropin-releasing hormone analogs upon replacement of histidine with substituted pyridinium,” Journal of Medicinal Chemistry 47, 6025-6033 (2004).
• Kem, W.R., Mahnir, V.M., Prokai, L., Papke, R.L., Cao, X., Le Francois, S., Wildeboer, K., Prokai-Tatrai, K., Porter-Papke, J., Soti, F. “Hydroxy metabolites of the Alzheimer's drug candidate DMXBA (GTS-21): Their molecular properties, interactions with brain nicotinic receptors, and brain penetration,” Molecular Pharmacology 65, 56-67 (2004).
• Prokai, L., Prokai-Tatrai, K., Perjesi, P., Zharikova, A.D., Perez, EJ., Liu, R., “Mechanistic interpretation of the hydroxyl radical detoxifying effect of estrogen and estrogen derivatives,“ Chemical Research in Toxicology 17 , 1775-1775 (2004).
• Prokai, L., Prokai-Tatrai, K., Perjesi, P., Zharikova, A.D., Perez, E.J., Liu, R. “Chemical shield mechanism for estrogen neuroprotection: Steroidal quinols as new molecular leads,“ Am. Chem. Soc. 225, U177-U178 (2003).
• Prokai L, Prokai-Tatrai K, Perjesi P, Zharikova AD, Simpkins JW. “Quinol-based metabolic cycle for estrogens in rat liver microsomes,“ Drug Metabolism and Disposition 31, 701-704 (2003).
• Prokai, L., Prokai-Tatrai, K., Perjesi, P., Zharikova, A.D., Perez, E.J., Liu, R. “Chemical shield mechanism for estrogen neuroprotection: Steroidal quinols as new molecular leads,“ Am. Chem. Soc. 225, 177-178 (2003).
• Prokai, L., Stevens, S.M., Prokai-Tatrai, K. “Chirality-based isotope labeling in library of substrates (CHILLS) to screen for enzyme preference by mass spectrometry,“ Biopolymers 71, 356-356 (2003).
• Prokai, L., Prokai-Tatrai, K., Perjesi, P., Zharikova, A.D., Perez, E., Liu, R., Simpkins, J.W. “Quinol-based cyclic antioxidant mechanism in estrogen neuroprotection,” Proceedings of the National Academy of Sciences of the United States of America 100, 11741–11746 (2003).
• Prokai-Tatrai, K., Nguyen, V., Zharikova, A.D., Braddy, A.C., Stevens, S.M. Jr., Prokai, L. “Prodrugs to enhance central nervous system effects of the TRH-like peptide pGlu-Glu-Pro-NH2,” Bioorganic & Medicinal Chemistry Letters 13, 1011-10014 (2003).
• Liu, R., Yang, S.-H., Perez, E., Yi, K.D., Wu, S.S., Eberst, K., Prokai, L., Prokai-Tatrai, K., Cai, Z.Y., Covey, D.F., Day, D.L., Simpkins, J.W. "Neuroprotective effects of a novel non-receptor binding estrogen analogue: in vitro and in vivo analysis," Stroke 33, 2485-2491 (2002).
• Kem, W., Mahnir, V., Prokai, L., Cao, X., Papke, R., Porter-Papke, J., Michalski, S., Wildeboer, K., Prokai-Tatrai, K., Soti, F. “Hydroxy metabolites of the Alzheimer's drug candidate DMXBA (GTS-21): A comparison of their chemical properties, brain penetration and interactions with brain nicotinic receptors,“ Neurobiology of Aging 23, S121-S122 (2002).
• Prokai-Tatrai, K., Perjesi, P., Zharikova, A.D., Li, X., Prokai, L. “Design, synthesis and biological evaluation of novel, centrally-acting thyrotropin-releasing hormone analogues,” Bioorganic & Medicinal Chemistry Letters 12, 2171-2174 (2002).
• Prokai, L., Zharikova, A., Janaky, T., Li, X., Braddy, A.C., Perjesi, P., Matveeva, L., Powell, D.H., Prokai-Tatrai, K. "Integration of mass spectrometry into early-phase discovery and development of central nervous system agents," Journal of Mass Spectrometry 36, 1211-1219 (2001).
• Prokai, L., Prokai-Tatrai, K., Zharikova, A.D., Li, X., Rocca, J.R. “Combinatorial lead-optimization of a neuropeptide FF antagonist,” Journal of Medicinal Chemistry 44, 1623-1626 (2001).
• Prokai, L., Oon, S.-M., Prokai-Tatrai, K., Abboud, K., Simpkins, J.W. “Synthesis and biological evaluation of 17β-alkoxyestra-1,3,5(10)-trienes as potential neuroprotectants against oxidative stress,” Journal of Medicinal Chemistry 44, 110-114 (2001).
• Prokai, L., Zharikova, A.D., Janaky, T., Prokai-Tatrai, K. “Exploratory pharmacokinetics and brain distribution study of a neuropeptide FF antagonist by liquid chromatography/atmospheric pressure ionization tandem mass spectrometry,” Rapid Communications in Mass Spectrometry 14, 2412-2418 (2000).
• Prokai, L., Prokai-Tatrai, K., and Bodor, N. “Targeting drugs to the brain by redox chemical delivery systems,“ Medicinal Research Reviews 20, 367-416 (2000).
• Prokai, L., Prokai-Tatrai, K., Ouyang, X., Wu, W.-M., Kim, H.-S., Zharikova, A., Bodor, N. “Metabolism-based brain-targeting system for a thyrotropin-releasing hormone analogue,” Journal of Medicinal Chemistry 42, 4563-4571 (1999).
• Prokai, L., Prokai-Tatrai, K. “Metabolism-based drug design and drug targeting,” Pharmaceutical Science & Technology Today 2, 457-462 (1999).
• Mahnir, V., Lin, B., Prokai-Tatrai, K., Kem, W.R. "Pharmacokinetics and urinary excretion of DMXBA (GTS-21), a compound enhancing cognition," Biopharmaceutics & Drug Disposition 19, 147-151 (1998).
• Prokai, L., Ouyang, X., Prokai-Tatrai, K., Simpkins, J.W., Bodor, N. "Synthesis and behavioral evaluation of a chemical brain-targeting system for a thyrotropin-releasing hormone analogue," European Journal of Medicinal Chemistry 33, 879-886 (1998).
• Bodor, N., Prokai-Tatrai, K., Koltai, E., Prokai, L. “Preparation of O-(3,3,8,10,10-pentamethyl-1,2-dithia-5,8-diaza-cyclodecan-5-yl)-ethyl-O-pivaloyloxymethylene-P-phenylphosphonate,” Organic Preparations and Procedures International 30, 485-489 (1998).
• Prokai-Tatrai, K., Prokai, L., Bodor, N. "Brain-targeting of a leucine-enkephaline analogue by retrometabolic design," Journal of Medicinal Chemistry 39, 4775-4782 (1996).
• Pop. E., Prokai-Tatrai, K., Brewster, M. E., Bodor, N. "Analogs of tryptophan," Organic Preparations and Procedures International 26, 715-718 (1994).
• Prokai-Tatrai, K., Zoltewicz, J.A., Kem, W.R. "Synthesis of a bridged anabasine and related compounds. Nuclear magnetic resonance spectroscopy and molecular modeling study," Tetrahedron 50, 9909-9918 (1994).
• Pop, E., Brewster, ME., Prokai-Tatrai, K., Bodor, N. “Novel redox derivatives of tryptophan,” Heterocycles 38, 2051-2064 (1994).
• Pop, E., Brewster, M.E., Prokai-Tatrai, K., Bodor, N. "Preparation of redox derivatives of 3 -hydroxy-5 -pregnane-11,20-dione," Organic Preparations and Procedures International 26, 296-300 (1993).
• Zoltewicz, J.A., Prokai-Tatrai, K., Bloom, L.B., Kem, W.R. "Long range transmission of polar effects in cholinergic 3-arylidene anabaseines. Conformations calculated by molecular modelling," Heterocycles 35, 171-179 (1993).
• Prokai, L., Prokai-Tatrai, K., Pop, E., Bodor, N., Lango, J., Roboz, J. "Fast atom bombardment and tandem mass spectrometry of quaternary pyridinium-substituted tryptophans," Organic Mass Spectrometry 28, 707-715 (1993).
• Pop, E., Anderson, W., Prokai-Tatrai, K., Vlasak,J., Brewster, M.E., Bodor, N. "Synthesis and preliminary pharmacological evaluation of some chemical delivery systems of 2,6-diisopropylphenol (Propofol)," Med. Chem. Res. 2, 16-21 (1992).
• Pop, E., Prokai-Tatrai, K., Anderson, W., Brewster, M.E., Bodor, N. "Redox analogs of centrally acting amines: design, synthesis and properties of a tranylcypromine derivative with potentially enhanced therapeutic index," Journal of Biopharmaceutical Sciences 2, 11-23 (1991).
• Prokai-Tatrai, K., Pop, E., Anderson, W., Lin, J.L., Brewster, M.E., Bodor, N. "Redox derivatives of tranylcypromine: Syntheses, properties and monoamine oxidase inhibitor activity of several chemical delivery systems," Journal of Pharmaceutical Sciences 80, 255-261 (1991).
• Pop, E., Prokai-Tatrai, K., Anderson, W., Bodor, N. "Redox analogs of centrally acting therapeutic agents," Pharmaceutical Research 7, 201-204 (1990).
• Pop, E., Prokai-Tatrai, K., Anderson, W., Lin, J.L., Brewster, M.E., Bodor, N. "Application of the brain specific chemical delivery system approach to tranylcypromine," European Journal of Pharmacology 183, 1909 (1990).
• Pop, E., Anderson, W., Prokai-Tatrai, K., Brewster. M.E., Fregly, M., Bodor, N. "Antihypertensive activity of redox derivatives of tryptophan," Journal of Medicinal Chemistry 33, 2216 -2221 (1990).
• Pop, E., Prokai-Tatrai, K., Scott, J.D., Brewster, M.E., Bodor, N. "Application of a brain targeting chemical delivery system to 9-amino-1,2,3,4-tetrahydroacridine," Pharmaceutical Research 7, 658-664 (1990).
• Prokai-Tatrai, K., Toros, S., Heil, B. "Hydroformylation of methylmethacrylate via 'in-situ' rhodium-phosphine catalysts," Journal of Organometallic Chemistry 332, 331-335 (1987).
• Prokai-Tatrai, K., Toros, S., Heil, B. "Hydroformylation of nitrogen containing cyclic olefins via 'in-situ' rhodium-phosphine catalysts," Journal of Organometallic Chemistry 315, 231-236 (1986).