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Lucjan Strekowski Professor, Organic Chemistry North American Editor for Heterocyclic Communications: An International Journal of Heterocyclic Communciations. Ph.D., Institute of Organic Chemistry, Polish Academy of Sciences, (1972) Dr. Lucjan Strekowski Department of Chemistry Georgia State University P.O. Box 4098 Atlanta, Georgia 30302-4098
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Organic and Bioorganic Synthesis
Work is focused on the development of novel, efficient, synthetic approaches
to important classes of compounds, improvements of existing synthetic methods,
and application of these chemistries to the synthesis of biologically active
molecules. The following projects are currently underway:
Synthesis of Non-nucleoside Anti-HIV-1 Agents. It was the researchers
of Georgia State University who showed for the first time that cationic
heteroaromatic compounds that intercalate with RNA are active against HIV-1.
To date several drug candidates have been developed that are active below
a concentration of 1æM and nontoxic to human cells in vitro at the
concentration of 100æM.
Fluorine-substituted compounds are of immense interest in medicinal chemistry.
Novel synthetic methods for the introduction of a fluorine atom into organic
molecules are being successfully developed in our laboratories.
Synthesis of New Cyanine Dyes for Bioanalytical Applications. A
highly successful work (in collaboration with G.
Patonay) is in progress to develop an ultrasensitive
analytical method for the determination of proteins including the HIV-1-
specific proteins in crude clinical isolates. The method utilizes cyanine
dyes as labels that fluoresce in the near- infrared (NIR) region. New chemistries
have been developed in our laboratories to synthesize NIR dyes substituted
with an isothiocyanato group. The isothiocyanato group reacts with an amino
group of the protein to form a stable thiourea linkage between the NIR
chromophore and the protein.
Diastereomeric Interactions of Chiral Molecules with DNA. Our group
has recently developed novel chemistries for a facile synthesis of chiral
DNA intercalators. The enantiomeric molecules exhibit substantially different
affinities toward B- DNA. Work is in progress to synthesize practical molecular
probes for recognition of DNA helicity (B-DNA and Z-DNA).
Stereoelectronic Factors in the Interaction with DNA of Groove-Binding
Molecules. Recently our group has shown for the first time that the
strength of the interaction of groove-binding molecules with DNA depends
on the direction and magnitude of polarization of the aromatic systems
of the molecules. Work is being continued, as this finding has important
ramifications for the design of biologically active agents that interact
with DNA.
Stabilization of the Triple-helix Structure of DNA. Novel compounds
that bind selectively with the triple-helix structure of DNA in the presence
of duplex DNA and RNA have been synthesized recently in our laboratories.
Work is being continued (in collaboration with W.D. Wilson) as this finding
has important ramifications for the design of biologically active agents
for the control of gene expression.
Synthesis of CNS Agents. Work is underway to synthesize compounds
that bind selectively to different sub-types of HT receptors. A practical
synthetic route to a novel, highly potent anti-migraine drug is currently
being developed in our laboratories.
Representative Publications
W.R. Winkeljohn, P.C. Vasquez, L. Strekowski & A.L. Baumstark (2004). Oxidation of Substituted Pyridines by Dimethyldioxirane: Kinetics and Solvent Effects, Tetrahedron Lett., 45 8295-8297.
Kim, N., ElKhalili, M., Henary, M.M., Strekowski, L., & Michniak, B.B. (1999). Percutaneous Penetration Enhancement Activity of Aromatic S,S-Dimethyliminosulfuranes. International Journal of Pharmaceutics 187, 219-229.
Snyder, R.D. & Strekowski, L. (1999). Enhancement of Bleomycin-Induced Micronucleus Formation in V79 Cells as a Rapid and Sensitive Screen for non-Covalent DNA-Binding Compounds. Mutation Research-Genetic Toxicology and Environmental Mutagenesis 444, 181-192.
Smith, J.C., Chandrasekaran, S. & Strekowski, L.S. (1999). Interaction of the Probe Oxonol V and the Drug Candidate LS8 with Small Unilamellar DMPC Vesicles. Biophysical Journal 76, A440.
Daneshvar, M.I., Peralta, J.M., Casay, G.A., Narayanan, N., Evans, L., Patonay, G., & Strekowski, L. (1999). Detection of Biomolecules in the Near-Infrared Spectral Region via a Fiber-Optic Immunosensor. Journal Of Immunological Methods 226, 119-128.
Strekowski, L., Zegrocka, O., Henary, M., Say, M., Mokrosz, M.J., Kotecka, B.M. Manzel, L., & Macfarlane, D.E. (1999). Structure-Activity Relationship Analysis of Substituted 4-Quinolinamines, Antagonists of Immunostimulatory CpG-Oligodeoxynucleotides. Bioorganic & Medicinal Chemistry Letters 9, 1819-1824.
Strekowski, L., Ismail, M.A., & Zoorob, H.H. (1999). Novel Synthetic Transformations of 5-(omega-Chloroalkanoyl)-1,3-Dimethylbarbituric Acids. Heterocyclic Communications 5, 107-110.
Strekowski, L., Henary, M., Kim, N., & Michniak, B.B. (1999). N-(4-Bromobenzoyl)-S,S-dimethyliminosulfurane, a Potent Dermal Penetration Enhancer. Bioorganic & Medicinal Chemistry Letters 9, 1033-1034.
Keppler, M., Zegrocka, O., Strekowski, L., & Fox, K.R. (1999). DNA Triple Helix Stabilisation by a Naphthylquinoline Dimer. Febs Letters 447, 223-226.
Strekowski, L., Ismail, M.A. & Zoorob, H.H. (1999). A General Method for Acylation of 1,3-Dialkyl-Substituted Barbituric and 2-Thiobarbituric Acids. Heterocyclic Communications 5, 9-10.
Parker, A.N. & Strekowski, L. (1998). An uUnusual 2,6-Dialkoxylation of Quinoline by the Reaction with Elemental Fluorine and Alcohol. Heterocyclic Communications 4, 493-496.
Abdou, I.M. Netzel, T.L. & Strekowski, L. (1998). Synthesis of N-6-(Anthraquinone-2''-carbonyl)-2'-deoxyadenosine. Heterocyclic Communications 4, 399-401.
Strekowski, L., Ismail, M.A. & Zoorob, H.H. (1998). Efficient Synthesis of 5-Perfluoroalkyl and 5-Perfluoroacyl-Substituted Uracils. Heterocyclic Communications 4, 387-391.
Lee, H.R., Czarny, A., Battiste, M.A. & Strekowski, L. (1998), Synthesis of Aminophenyl and Methoxyphenyl Perfluoroalkyl Ketones. Journal of Fluorine Chemistry 91, 221-224.
Tarazi, L., George, A., Patonay, G. & Strekowski, L. (1998). Spectral Characterization of a Novel Near-Infrared Cyanine Dye: a Study of Its Complexation with Metal Ions. Talanta 46, 1413-1424.
Strekowski, L., Lin, S.Y., Lee, H., Zhang, Z.Q. & Mason, J.C. (1998). Synthesis of 4-Perfluoroalkylquinolines. Tetrahedron 54, 7947-7954.
Strekowski, L., Zegrocka, O., Windham, C. & Czarny, A. (1997). Practical Synthesis of 4-Chloro-2-(2-naphthyl)quinoline, a Precursor to Triple-Helix DNA Intercalators. Organic Process Research & Development 1, 384-386.
Battiste, M.A., Strekowski, L. & Paryzek, Z. (1997). Synthetic Pathways to 2,2-Dimethyl-6-oxo-1-cyclohexaneacetic acid, a Useful Isoprenoid Building Block. Organic Process Research & Development 1, 222-225.
Czarny, A., Lee, H., Say, M. & Strekowski, L. (1997). A Novel Synthesis of 4-Perfluoroalkylquinolines and Related Substituted Quinolines. Heterocycles 45, 2089-2092.
Mason, J.C., Patonay, G. & Strekowski, L. (1997). A New pH-Sensitive Near-Infrared chromophore. Heterocyclic Communications 3, 409-411.
Strekowski, L. & Lin, S.Y. (1997). Studies on Isoxazole and Pyrazole Formation by the Reaction of Trifluoromethyl-Substituted Anilines with Oxime and Hydrazone Dianions. Journal Of Heterocyclic Chemistry 34, 1625-1627.
Lee, S.K., Richter, M.M., Strekowski, L. & Bard, A.J. (1997). Electrogenerated Chemiluminescence .61. Near-IR Electrogenerated Chemiluminescence, Electrochemistry, and Spectroscopic Properties of a Heptamethine Cyanine Dye in MeCN. Anal.Chem. 69, 4126-4133.
Williams, R.J., Peralta, J.M., Tsang, V.C.W., Narayanan, N., Casay, G.A., Lipowska, M., Strekowski, L. & Patonay, G. (1997). Near-Infrared Heptamethine Cyanine Dyes: A New Tracer for Solid-Phase Immunoassays. Applied Spectroscopy 51, 836-843.
Abdou, I.M., Strekowski, L., AbdelMegeed, M.F., Attia, A.M.E. & Omara, M.A. (1997). Synthesis of 1-(beta-D-Blucopyranosyl)pyrimidin-2(1H)-ones from 2-Chloropyrimidines. Heterocyclic Communications 3, 295-300.
Mokrosz, M.J., Duszynska, B., Klodzinska, A., DerenWesolek, A., ChojnackaWojcik, E., Baranowski, T.C., Abdou, I.M., Redmore, N.P. & Strekowski, L. (1997). 4-(3-Furyl)-2-(4-methylpiperazino)pyrimidines: Potent 5-HT2A Receptor Antagonists. Bioorganic & Medicinal Chemistry Letters 7, 1635-1638.
Hofstraat, J.W., vanHouwelingen, G.D.B., Schotman, A.H.M., Nuijens, M.J., Gooijer, C., Velthorst, N.H., Strekowski, L. & Patonay, G. (1997). Near-IR Fluorescent Labels for Determination of Functional Groups in Polymeric Materials. Polymer 38, 4033-4041.
Strekowski, L., Janda, L. & Lee, H. (1997). Synthesis of bis(2-Arylquinolin-4-yl)amines by Lithium bis(Trimethylsilyl) Amide-Mediated Cyclization of Ketimines Derived from 2-(Trifluoromethyl)anilines and Aryl Methyl Ketones. J.Org.Chem. 62, 4193-4196.
Strekowski, L., Lin, S.Y., Lee, H., Wydra, R.L. & Kiselyov, A.S. (1997). Chemistry of the Anionically Activated Perfluoroalkyl Group in Heterocyclic Synthesis. Heterocyclic Communications 3, 109-113.
Lin, S.Y., Hojjat, M. & Strekowski, L. (1997). A Facile Synthesis of 4-(Trialkylmethyl)anilines by the Reaction of 4-(trifluoromethyl)aniline with Grignard Reagents. Synthetic Communications 27, 1975-1980.
Swamy, A.R., Danesvar, M.I., Evans, L., Strekowski, L., Narayanan, N., Szurdoki, F., Wengatz, I., Hammock, B.D. & Patonay, G. (1997). Near-Infrared Fluorescent Immunoassays: A Novel Approach to Environmental Analysis. Acs Symposium Series 657, 146-161.
Patterson, S.E., Coxon, J.M. & Strekowski, L. (1997). Intercalation of Ethidium and Analogues with Nucleic Acids: A Molecular Orbital Study. Bioorganic & Medicinal Chemistry 5, 277-281.
Narayanan, N., Strekowski, L., Lipowska, M. & Patonay, G. (1997). A New Method for the Synthesis of Heptamethine Cyanine Dyes: Synthesis of New Near Infrared Fluorescent Labels. (vol 60, pg 2391, 1995). J.Org.Chem. 62, 9387-9387.
Strekowski, L., Lipowska, M., Gorecki, T., Mason, J.C. & Patonay, G. (1996). Functionalization of Near-Infrared Cyanine dyes. Journal Of Heterocyclic Chemistry 33, 1685-1688.
Gorecki, T., Patonay, G., Strekowski, L., Chin, R. & Salazar, N. (1996). Synthesis of Novel Near-Infrared Cyanine Dyes for Metal Ion Determination. Journal Of Heterocyclic Chemistry 33, 1871-1876.
Mokrosz, J.L., Duszynska, B., CharakchievaMinol, S., Bojarski, A.J., Mokrosz, M.J., Wydra, R.L., Janda, L. & Strekowski, L. (1996). Structure-Activity Relationship Studies of CNS Agents .29. N- Methylpiperazino-Substituted Derivatives of Guinazoline, Phthalazine and Quinoline as Novel alpha(1), 5-HT1A and 5-HT2A Receptor Ligands. European Journal Of Medicinal Chemistry 31, 973-980.
Cassidy, S.A., Strekowski, L. & Fox, K.R. (1996). DNA Sequence Specificity of a Naphthylquinoline Triple Helix- Binding Ligand. Nucleic Acids Research 24, 4133-4138.
"Base-Mediated Reactions of ortho-Perfluoroalkylanilines and para-Perfluoroalkylanilines", Strekowski, L.; Lin, S. Y.; Lee, H.; Mason, J. C.; Tetrahedron Lett. 1996, 37, 4655.
"Amination by Lithium Alkylamide Reagents of Ketimines Derived from 2-(Trifluoromethyl)anilines: Methyl Halophenyl Ketones and Their Cyclization Products 2-(Halophenyl)quinolin-4-amines", Strekowski, L.; Janda, L.; Patterson, S. E.; Nguyen, J. Tetrahedron 1996, 52, 3273.
Strekowski, L., Gulevich, Y., Baranowski, T.C., Parker, A.N., Kiselyov, A.S., Lin, S.Y., Tanious, F.A. & Wilson, W.D. (1996). Synthesis and Structure-DNA Binding Relationship Analysis of DNA Triple-Helix Specific Intercalators. Journal Of Medicinal Chemistry 39, 3980-3983.
Battiste, M.A., Wydra, R.L. & Strekowski, L. (1996). Efficient and Stereoselective Synthesis of 10-Hydroxy-4,8- Dimethyldeca-3(E),8(E)-Dienoic acid, a Precursor to (3E,8E)- Suspensolide, Anastrephin, and Epianastrephin. J.Org.Chem. 61, 6454-6455.
Mokrosz, J.L., Bojarski, A.J., Harden, D.B. & Strekowski, L. (1996). Conformational Analysis of 4-(2'-Furyl)-2- (Methylamino)pyrimidine. i Journal Of Heterocyclic Chemistry 33, 1207-1210.
"Synthesis, Chromatographic-Separation, and Characterization of Near-Infrared-Labeled DNA Oligomers for use in DNA-Sequencing", Shealy, D. B.; Lipowska, M.; Lipowski, J.; Narayanan, N.; Sutter, S.; Strekowski, L.; Patonay, G. Anal. Chem. 1995, 67, 247.
"A Facile Synthesis of 2-Substituted N-tert-Butoxycarbonyl-N-methyl-1,3-propanediamines, Key Intermediates for the Preparation of Triplex DNA-Specific Intercalators", Strekowski, L.; Gulevich, Y.; Vanaken, K.; Wilson, D. W.; Fox, K. Tetrahedron Lett. 1995, 36, 225.
"Experimental and Computational Studies of Trifluoromethylation of Aromatic-amines by the System Trifluoroiodomethane Zinc Sulfur-Dioxide", Strekowski, L.; Hojjat, M.; Patterson, S. E.; Kiselyov, A. S.; J. Heterocycl. Chem. 1994, 31, 1413.