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Laszlo Prokai , Ph.D.
Robert A. Welch Professor
Department: Molecular Biology and Immunology
Office: RES 466
Phone: 817-735-2206
Email: lprokai@hsc.unt.edu
Faculty Homepage

 

Biographical Sketch | Education | 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 was selected as the first Robert A. Welch Professor of Chemistry at the Department of Molecular Biology & Immunology of the University of North Texas Health Science Center in 2005. He is an Adjunct Professor at the Department of Medicinal Chemistry, University of Florida, 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 Medicine Chemistry, Central Nervous System Agents in Medicinal Chemistry, Current Drug Delivery, Medicinal Chemistry Reviews-Online and Medicinal Chemistry.

Research Interests
Dr. Prokai’s current research focuses on
(1) Understanding the mechanisms by which estrogens erect a "chemical shield" to protect neurons against reactive species and exploring novel therapies to treat neurodegenerative and ophthalmic diseases from the findings. Dr. Prokai's laboratory has made several important discoveries recently, including a novel antioxidant cycle involving a unique class of compounds called para-quinols as key products.
(2) Development and use of proteomics in aging research, studying neurodegenerative diseases and in biodefense.
(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 three mass spectrometers.

Education

B.Sc. 1978 Chemical Engineering; Summa Cum Laude, University of Veszprem, Veszprem,Hungary
M.Sc. 1980 Chemical Engineering (Radiochemical Technology); Summa Cum Laude, University of Veszprem, Veszprem, Hungary
Ph.D. 1983 Radiochemistry; Summa Cum Laude, University of Veszprem, 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)
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)
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):280-88.

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):1583-89.

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.

Perjési 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
Prodrugs for Use as Ophthalmic Agents, US Patent 7,534,779

Awards and Honors
Candidate of Science in Chemistry (C.Sci), Hungarian Academy of Sciences in 1987
Habilitation (Dr. habil.) by the University of Veszprém in 2000
Leading Scientist of the World 2006, International Biographical Centre, Cambridge, England