Biographical Sketch | Education | Publications | Patents | Awards and Honors

Biographical Sketch

Dr. Prokai started his academic career as an Assistant Professor at the Department of Pharmaceutics and the Center for Drug Discovery of the College of Pharmacy at the University of Florida in 1991. During his tenure there, he rose in rank to Professor in the Department of Medicinal Chemistry, held an Affiliate Professorship at the Department of Chemistry, was a Joint Professor of the Department of Anesthesiology, Scientific Advisor of the Biotechnology Program, and Member of the McKnight Brain Institute. Dr. Prokai joined the Department of Molecular Biology & Immunology of the University of North Texas Health Science Center in 2005. He is currently Professor and the Robert A. Welch Chair in Biochemistry. Dr. Prokai also is Courtesy Professor at the Department of Medicinal Chemistry, University of Florida, and Adjunct Professor at the Department of Chemistry and Biochemistry, University of Texas at Arlington and at the Department of Chemistry of the Texas Christian University. Dr. Prokai has maintained an actively funded research program supported by the National Institutes of Health (NIH) and is recognized nationally and internationally for his work on discovery, bioorganic and medicinal chemistry of central nervous system agents, as well as on neuropeptides, proteomics and mass spectrometry. Dr. Prokai has been an invited speaker on numerous national and international scientific meetings, received a Pro Renovanda Cultura Hungariae Visiting Professorship at the Department of Medical Chemistry, University of Szeged (Hungary) in 2002, and has been an active collaborator with pharmaceutical and chemical companies. He currently serves on the Editorial Boards of Current Medicinal Chemistry, Central Nervous System Agents in Medicinal Chemistry, Current Drug Delivery, Medicinal Chemistry Reviews-Online, Medicinal Chemistry, Journal of Data Mining in Genomics & Proteomics and the Journal of Integrated Omics.

Research Interests
Dr. Prokai's current research focuses on
(1) Novel therapies against neurodegenerative and ophthalmic diseases using site-selective prodrugs.
(2) Development and use of proteomics in aging research, studying neurodegenerative diseases and cancer, with especial attention to quantitative expression profiling and oxidative stress-associated posttranslational modifications.
(3) Discovering new therapeutic agents based on neuropeptides and peptidomimetics as lead molecules.
These multidisciplinary projects rely on his broad technical expertise in state-of-the-art methods in bioorganic, medicinal and bioanalytical chemistry, and on excellent facilities featuring four mass spectrometers.

Education

B.Sc. 1978 Chemical Engineering; Summa Cum Laude, University of Veszprem (now University of Pannonia), Veszprem,Hungary
M.Sc. 1980 Chemical Engineering (Radiochemical Technology); Summa Cum Laude, University of Veszprem (now University of Pannonia), Veszprem, Hungary
Ph.D. 1983 Radiochemistry; Summa Cum Laude, University of Veszprem (now University of Pannonia), Veszprem, Hungary
Postdoctoral training in Medicinal Chemistry, 1987 to 1989; Department of Medicinal Chemistry, University of Florida, Gainesville, FL

Publications
Monograph
Prokai L. Field Desorption Mass Spectrometry, Practical Spectroscopy Monograph Series, Marcel Dekker, New York, 1990, pp. 304.

Book Edited
Prokai L, Prokai-Tatrai K. Peptide Transport and Delivery Into the Central Nervous System, Progress in Drug Research, Vol. 61, Birkhäuser, Basel, 2003, pp. 245.

Selected Book Chapters (Recent)
Rauniyar N, Prokai L. Mass spectrometry-based methods to investigate posttranslational protein modifications by lipid-peroxidation products, in Handbook of Mass Spectrometry (M. Lee, Ed.), John Wiley & Sons, Chichester, UK, 2012, 23-40.

Prokai-Tatrai K, Prokai L. Prodrugs for brain delivery of small neuropeptides, Chapter 21 in Neuropeptides: Methods and Protocols (A. Merighi, Ed.), Methods in Molecular Biology, Vol. 789, Humana–Springer, Totowa, NJ, 2011, 313-336.

Prokai L. Application of mass spectrometry in brain research: neurotransmitters, neuropeptides, and brain proteins, in Medical Applications of Mass Spectrometry (K. Vekey, A. Telekes, A. Vertes, Eds.), Elsevier, Amsterdam, 2008, 407-424.

Prokai-Tatrai K, Prokai L. The impact of metabolism on the safety of estrogen therapy, in the Annals of the New York Academy of Sciences, Vol. 1052 (M. Singh, Ed.), New York Academy of Sciences, New York, NY, 2005, 243-257.

Prokai L, Stevens SM, Simonsick W. Size-exclusion chromatography coupled to mass spectrometry and tandem mass spectrometry for oligomer analysis, in Multiple Detection in Size-Exclusion Chromatography (A.M. Striegel, Ed.), ACS Books, Washington, DC, 2005, 196-207.

Prokai-Tatrai K, Prokai L. Modifying peptide properties by prodrug design for enhanced transport into the CNS. Prog Drug Res.2003 Jan;61(1):155-88.

Selected Peer-Reviewed Papers (Recent)
Guo J, Prokai L. Conversion of 3-nitrotyrosine to 3-aminotyrosine residues facilitates mapping of tyrosine nitration in proteins by electrospray ionization–tandem mass spectrometry using electron capture dissociation. J Mass Spectrom., accepted for publication.

Bernal-Perez L, Prokai L, Ryu Y. Selective N-terminal fluorescent labeling of proteins using NBD-Cl: a method to distinguish protein N-terminal acetylation. Anal Biochem. 2012 September;428(1):13-15.

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. J Chromatogr A. 2012 April;232(1):281-287.

Guo J, Prokai-Tatrai K, Prokai L. Differential quantitation of protein nitration by liquid chromatography-mass spectrometry using isotope-coded dimethyl labeling and chemoprecipitation. J Chromatogr A. 2012 April;1232(1):266-275.

Bernal-Perez L, Sahyouni F, Prokai L, Ryu Y. Context-dependent N-terminal acetylation of the recombinant Z-domain protein in Escherichia coli. Mol Biosystems. 2012 April;8(4):1128-1130.

Rauniyar N, Prokai L. Isotope-coded dimethyl tagging for differential quantification of posttranslational protein carbonylation by 4-hydroxy-2-nonenal, an end-product of lipid peroxidation. J Mass Spectrom. 2011 October;46(10):976-985.

Braden BB, Garcia AN, Mennenga SE, Prokai L, Villa SR, Acosta J, Lefort N, Simard AR, Bimonte-Nelson HA. Cognitive impairing effects of medroxyprogesterone acetate has long-lasting detrimental effects on spatial cognition in the rodent: independent and interactive effects across time. Psychopharmacology. 2011 November;218(2):405-418.

Guo J, Prokai-Tatrai K, Nguyen V, Rauniyar N, Ughy B, Prokai L. Protein targets for carbonylation by 4-hydroxy-2-nonenal in rat liver mitochondria. J Proteomics. 2011 October;74(11):2370-2379.

Guo J, Prokai L. To tag or not to tag: A comparative evaluation of immunoaffinity-labeling and tandem mass spectrometry for the identification and localization of posttranslational protein carbonylation by 4-hydroxy-2-nonenal, an end-product of lipid peroxidation. J Proteomics. 2011 October;74(11):2360-2369.

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. Mol Cell Proteomics. 2012 August;10(10):10.1074/mcp.M110.002923,1-10

Nagaprashantha LD, Vatsyayan R, Singhal J, Lelsani P, Prokai L, Awasthi S, Singhal SS. 2’-Hydroxyflavanone inhibits proliferation, tumor vascularization and promotes normal differentiation in VHL-mutant renal cell carcinoma. Carcinogenesis. 2011 April;32(4):568-575.

Shahzad MMK, Mangala LS, Han HD, Lu C, Bottsford-Miller J, Mora EM, Lee JW, Stone RL, Thanapprapasr D, Roh JW, Gaur P, Nair MP, Park YY, Sabnis N, Lee JS, Ellis LM, Lopez-Berestein G, McConathy WJ, Prokai L, Lacko AG, Sood AK. Targeted delivery of small interfering RNA using rHDL nanoparticles. Neoplasia. 2011 April;13(4):309-319.

Engler-Chiurazzi E, Tsang C, Nonnenmacher S; Liang S, Corneveaux J, Prokai L, Huentelman M, Bimonte-Nelson HA. Tonic Premarin dose-dependently enhances memory, affects neurotrophin protein and alters gene expression in middle-aged rats. Neurobiol Aging. 2011 April;32(4):680-697.

Talboom J, Engler-Chiurazzi E, Whiteaker P, Simard A, Lukas R, Acosta J, Cosand M,Prokai L, Bimonte-Nelson HA. A component of Premarin enhances multiple cognitive functions and influences nicotinic receptor expression. Horm Behav. 2010 November;58(5):917-928.

Chaudhary P, Sharma R, Sharma A, Vatsyayan R, Yadav S, Singhal SS, Rauniyar N, Prokai L, Awasthi S, Awasthi YC. Mechanisms of 4-Hydroxy-2-nonenal induced pro- and anti-apoptotic signaling. Biochemistry. 2010 June;49(22):6263-75.

Nguyen V, Zharikova AD, Prokai-Tatrai K, Prokai L. [Glu²]TRH dose-dependently attenuates TRH-evoked analeptic effect in the mouse brain. Brain Res Bull. 2010 April;82(1-2):83-6.

Rauniyar N, 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. J Mass Spectrom. 2010 April;45(4):398-410.

Braden BB, Talboom JS, Crain I, Simard AR, Lukas RJ, Prokai L, Scheldrup M, Bowman B, Bimonte-Nelson HA. The WHI progestin, medroxyprogesterone acetate, impairs memory and alters the GABAergic system in aged surgically menopausal rats. Neurobiol Learn Mem. 2010 March;93(3):444-53.

Laczko-Dobos H, Frycak P, Ughy B, Domonkos I, Wada H, Prokai L, Gombos Z. Remodeling of phosphatidylglycerol in Synechocystis PCC6803. Biochim Biophys Acta - Mol Cell Biol Lipids. 2010 February; 1801(2):163-70.

Prokai-Tatrai K, Bonds D, Prokai L. Simultaneous measurement of 17beta-estradiol, 17alpha-estradiol and estrone by GC - isotope dilution MS/MS. Chromatographia. 2010 February; 71:311-5.

Rauniyar N, Prokai L. Detection and identification of 4-hydroxy-2-nonenal Schiff-base adducts along with products of Michael addition using data-dependent neutral loss-driven MS³ acquisition: method evaluation through an in vitro study on cytochrome c oxidase modifications. Proteomics. 2009 December; 9(22):5188-93.

Dasgupta S, Wasson L, Rauniyar N, Prokai L, Borejdo J, Vishwanatha JK. Novel gene C17orf37 in 17q12 amplicon promotes migration and invasion of prostate cancer cells. Oncogene. 2009 August 13; 28(32):2860-72.

Prokai L, Stevens SM, Rauniyar N, Nguyen V. Rapid label-free identification of estrogen-induced differential protein expression in vivo from mouse brain and uterine tissue. J Proteome Res. 2009 August; 8(8):3862-71.

Kocsis B, Kustos I, Kilar F, Nyul A, Jakus PB, Kerekes S, Villarreal V, Prokai L, Lorand T. Antifungal unsaturated cyclic Mannich ketones and amino alcohols: study of mechanism of action. Eur J Med Chem. 2009 May;44(5):1823-9.

Prokai-Tatrai K, Prokai L. Prodrugs of thyrotropin-releasing hormone and related peptides as central nervous system agents. Molecules. 2009 February; 14(2):633-54.

Rauniyar N, Stevens 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. Anal Chem. 2009 Jan;81(2):782-9.

Stevens SM, Prokai-Tatrai K, Prokai L. Factors that contribute to the misidentification of tyrosine nitration by shotgun proteomics. Mol Cell Proteomics. 2008 Dec;7(12):2442-51.

Prokai L, Frycak P, Stevens SM, Nguyen V. Measurement of acetylcholine in rat brain microdialysates by LC-isotope dilution tandem MS. Chromatographia. 2008 Oct;68:S101-5.

Nguyen V, Bonds DV, Prokai L. Measurement of hydroxyl-radical formation in the rat striatum by in vivo microdialysis and GC-MS. Chromatographia. 2008 Oct;68:S57-S62.

Prokai-Tatrai K, Kim HS, Prokai L. The utility of oligopeptidase in brain-targeting delivery of an enkephalin analogue by prodrug design. Open Med Chem J. 2008 Sept;2:97-100.

Stevens SM, Duncan RS, Koulen P, Prokai L. Proteomic analysis of mouse brain microsomes: identification and bioinformatic characterization of endoplasmic reticulum proteins in the mammalian central nervous system. J Proteome Res. 2008 March;7(3):1046-54.

Prokai-Tatrai K, Perjesi P, Rivera-Portalatin NM, Simpkins JW, Prokai L. Mechanistic investigations on the antioxidant action of a neuroprotective estrogen derivative. Steroids. 2008 March;73(3):280-8.

Stevens SM, Rauniyar N, Prokai L. Rapid characterization of covalent modifications to rat brain mitochondrial proteins after ex vivo exposure to 4-hydroxy-2-nonenal by liquid chromatography-tandem mass spectrometry using data dependent and neutral loss-driven MS³ acquisition. J Mass Spectrom. 2007 Dec;42(12):1599-1605.

Prokai L, Yan LJ, Vera-Serrano JL, Stevens SM, Forster MJ. Mass spectrometry-based survey of age-associated protein carbonylation in rat brain mitochondria. J Mass Spectrom. 2007 Dec;42(12):1583-9.

Branca RMM, Bodo G, Bagyinka C, Prokai L. De novo sequencing of a 21-kDa cytochrome c4 from Thiocapsa roseopersicina by nanoelectrospray ionization ion-trap and Fourier-transform ion-cyclotron resonance mass spectrometry. J Mass Spectrom. 2007 Dec;42(12):1569-82.

Rauniyar N, Stevens SM, Prokai L. Fourier transform ion cyclotron resonance mass spectrometry of covalent adducts of protein and 4-hydroxy-2-nonenal, a reactive end-product of lipid peroxidation. Anal Bioanal Chem. 2007 Nov;389(5):1421-8.  

Rivera-Portalatin NM, Serrano-Vera JL, Prokai-Tatrai K, Prokai L. Comparison of estrogen-derived ortho-quinone and para-quinol concerning induction of oxidative stress. J Steroid Biochem Mol Biol. 2007 June-July;105(1-5):71-5.

Prokai-Tatrai K, Rivera-Portalatin N, Rauniyar N, Prokai L. A facile microwave-assisted synthesis of p-quinols by lead(IV) acetate oxidation. Lett Org Chem. 2007 June;4(4):265-7.

Teixido M, Prokai-Tatrai K, Wang X, Nguyen V, Prokai L. Exploratory neuropharmacological evaluation of a bridged thyrotropin-releasing hormone analogue. Brain Res Bull. 2007 June;73(1-3):103-7.

Yan LJ, Yang SH, Shu H, Prokai L, Forster MJ. Histochemical staining and quantification of dihydrolipoamide dehydrogenase diaphorase activity using blue native PAGE. Electrophoresis. 2007 April; 28(7):1036-45.

Prokai L, Simpkins JW. Structure–nongenomic neuroprotection relationship of estrogens and estrogen-derived compounds. Pharmacol Therapeut. 2007 April;114(1):1-12.

Nguyen V, Zharikova AD, Prokai L. Evidence for interplay between thyrotropin-releasing hormone (TRH) and its structural analogue pGlu-Glu-Pro-NH₂ ([Glu²]TRH) in the brain: An in vivo microdialysis study. Neurosci Lett. 2007 March;415(1):64-7.

Prokai L, Zharikova AD, Juhasz A, Prokai-Tatrai K. Cardiovascular effects of neuropeptide FF antagonists. Peptides. 2006 May;27(5):1015-9.

Prokai L, Prokai-Tatrai K, Perjesi P, Simpkins JW. Mechanistic insights into the direct antioxidant effects of estrogens. Drug Dev Res. 2005 Oct;66(6):118-25.

Stevens SM, Chung AY, Chow MC, McClung SH, Strachan CN, Harmon AC, Denslow ND, Prokai L. Enhancement of phosphoprotein analysis using a fluorescent affinity tag and mass spectrometry. Rapid Commun Mass Spectrom. 2005 Jun;19(15):2157-62.

Bergeron RJ, Bharti N, Wiegand J, McManis JS, Yao H, Prokai L. Polyamine-vectored iron chelators: the role of charge. J Med Chem. 2005 Jun;48(12):4120-37.

Prokai-Tatrai K, Teixido M, Nguyen V, Zharikova AD, Prokai L. A pyridinium-substituted analogue of the TRH-like tripeptide pGlu-Glu-Pro-NH2 and its prodrugs as central nervous system agents. Med Chem. 2005 March;1(2):141-52.

Simpkins JW, Wang J, Wang X, Perez E, Prokai L, Dykens JA. Mitochondria play a central role in estrogen-induced neuroprotection. Curr Drug Targets CNS Neurol Disord. 2005 Feb;4(1):69-83.

Prokai L, Zharikova AD, Stevens SM. Effect of chronic morphine exposure on the synaptic plasma-membrane subproteome of rats: a quantitative protein profiling study based on isotope-coded affinity tags and liquid chromatography/mass spectrometry. J Mass Spectrom. 2005 Feb;40(2):169-75.

Stevens Jr SM, Prokai-Tatrai K, Prokai L. Screening of combinatorial libraries for substrate preference by mass spectrometry. Anal Chem. 2005 Jan;77(2):698-701.

Prokai L, Prokai-Tatrai K, Zharikova AD, Nguyen V, Perjesi P, Stevens SM. Centrally acting and metabolically stable thyrotropin-releasing hormone analogues by replacement of histidine with substituted pyridinium. J Med Chem. 2004 Nov;47(24):6025-33.

Yang SH, Liu R, Perez EJ, Wen Y, Stevens SM, Valencia T, Brun-Zinkernagel AM, Prokai L, Will Y, Dykens J, Koulen P, Simpkins JW. Mitochondrial localization of estrogen receptor beta. Proc Natl Acad Sci U S A. 2004 Mar;101(12):4130-5.

Ross BP, Braddy AC, McGeary RP, Blanchfield JT, Prokai L, Toth I. Micellar aggregation and membrane partitioning of bile salts, fatty acids, sodium dodecyl sulfate, and sugar-conjugated fatty acids: correlation with hemolytic potency and implications for drug delivery. Mol Pharm. 2004 Jan;1(3):233-45.

Kem WR, Mahnir VM, Prokai L, Papke RL, Cao X, LeFrancois S, Wildeboer K, Prokai-Tatrai K, Porter-Papke J, Soti F. Hydroxy metabolites of the Alzheimer's drug candidate 3-[(2,4-dimethoxy)benzylidene]-anabaseine dihydrochloride (GTS-21): their molecular properties, interactions with brain nicotinic receptors, and brain penetration. Mol Pharmacol. 2004 Jan;65(1):56-67.

Stevens SM, Zharikova AD, Prokai L. Proteomic analysis of the synaptic plasma membrane fraction isolated from rat forebrain. Brain Res Mol Brain Res. 2003 Oct;117(2):116-28.

Prokai L, Prokai-Tatrai K, Perjesi P, Zharikova D, Perez J, Liu R, Simpkins JW. Quinol-based cyclic antioxidant mechanism in estrogen neuroprotection. Proc Natl Acad Sci U S A. 2003 Sep;100(20):11741-6.

Prokai L, Prokai-Tatrai K, Perjesi P, Zharikova AD, Simpkins JW. Quinol-based metabolic cycle for estrogens in rat liver microsomes. Drug Metab Dispos. 2003 Jun;31(6):701-4.

Perjesi P, Kim T, Zharikova AD, Li X, Ramesh T, Ramasubbu J, Prokai L. Determination of clodronate content in liposomal formulation by capillary zone electrophoresis. J Pharm Biomed Anal. 2003 Apr;31(5):929-35.

Prokai-Tatrai K, Nguyen V, Zharikova AD, Braddy AC, Stevens SM, Prokai L. Prodrugs to enhance central nervous system effects of the TRH-like peptide pGlu-Glu-Pro-NH₂. Bioorg Med Chem Lett. 2003 Mar;13(6):1011-4.

Patents
Antagonists of RF-Amide Neuropeptides, US Patent 6,797,707
Antagonists of RF-Amide Neuropeptides, US Patent 6,960,574
Steroidal Quinols and Their Use for Antioxidant Therapy, US Patent 7,026,306
Thyrotropin-releasing hormone analogues and their therapeutic applications, US Patent 7,067,257
Prodrugs for Use as Ophthalmic Agents, US Patent 7,186,707
Steroidal Quinols and Their Use for Estrogen Replacement Therapy, US Patent 7,300,926
Quinol Compound and Pharmaceutical Composition, US Patent 7,534,779
Prodrugs for Use as Ophthalmic Agents, US Patent 7,572,781

Awards and Honors
Candidate of Science in Chemistry (C.Sci), by the Hungarian Academy of Sciences in 1987
Habilitation (Dr. habil.) by the University of Veszprem in 2000
Leading Scientist of the World 2006, International Biographical Centre, Cambridge, England
Doctor Academiae Scientiarum Hungaricae (D.Sc.) by the Hungarian Academy of Sciences in 2010