research overview
- We are developing redox active nucleotides that will allow electrically switchable DNA structures and electrically powered nano machines.
- Contact Info
Kuchta, Robert Professor
Positions
- Professor, Biochemistry
Research Areas
Research
keywords
- Nanomachines, DNA, Replication, Kinetics, Nanotechnology
Publications
selected publications
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conference proceeding
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journal article
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Synthesis of Small-Molecule/DNA Hybrids through On-Bead Amide-Coupling Approach.
Journal of Organic Chemistry.
10803-10811.
2017
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Protein Displacement by Herpes Helicase-Primase and the Key Role of UL42 during Helicase-Coupled DNA Synthesis by the Herpes Polymerase.
Biochemistry.
2651-2662.
2017
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Effects of Acyclovir, Foscarnet, and Ribonucleotides on Herpes Simplex Virus-1 DNA Polymerase: Mechanistic Insights and a Novel Mechanism for Preventing Stable Incorporation of Ribonucleotides into DNA.
Biochemistry.
1168-1177.
2016
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Polymerase and Exonuclease Activities in Herpes Simplex Virus Type 1 DNA Polymerase Are Not Highly Coordinated.
Biochemistry.
240-249.
2015
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Functionalized Tricyclic Cytosine Analogues Provide Nucleoside Fluorophores with Improved Photophysical Properties and a Range of Solvent Sensitivities.
Chemistry - A European Journal.
2010-2015.
2014
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The DNA helicase-primase complex as a target for herpes viral infection.
Expert Opinion on Therapeutic Targets.
1119-1132.
2013
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The Energetic Difference between Synthesis of Correct and Incorrect Base Pairs Accounts for Highly Accurate DNA Replication.
Journal of the American Chemical Society.
1205-1208.
2013
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Identification and Mechanistic Studies of a Novel Ubiquitin E1 Inhibitor.
Journal of Biomolecular Screening.
421-434.
2012
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Largazole and Its Derivatives Selectively Inhibit Ubiquitin Activating Enzyme (E1).
PLoS ONE.
2012
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Effect of transition metal ions on the fluorescence and Taq-catalyzed polymerase chain reaction of tricyclic cytidine analogs.
Analytical Biochemistry.
53-60.
2011
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B Family DNA Polymerases Asymmetrically Recognize Pyrimidines and Purines.
Biochemistry.
7243-7250.
2011
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Coordinated Leading and Lagging Strand DNA Synthesis by Using the Herpes Simplex Virus 1 Replication Complex and Minicircle DNA Templates.
Journal of Virology.
957-967.
2011
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Herpes Simplex Virus Type 1 Helicase-Primase: DNA Binding and Consequent Protein Oligomerization and Primase Activation.
Journal of Virology.
968-978.
2011
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Low-density microarrays for the detection of Borrelia burgdorferi s.s. (the Lyme disease spirochete) in nymphal Ixodes scapularis.
Ticks and Tick-borne Diseases.
27-36.
2011
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Cellular Abundance of Mps1 and the Role of Its Carboxyl Terminal Tail in Substrate Recruitment.
Journal of Biological Chemistry.
38730-38739.
2010
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Regulation of Influenza RNA Polymerase Activity and the Switch between Replication and Transcription by the Concentrations of the vRNA 5 ' End, the Cap Source, and the Polymerase.
Biochemistry.
10208-10215.
2010
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Mechanism and evolution of DNA primases.
BBA - Proteins and Proteomics.
1180-1189.
2010
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Photoinitiator Nucleotide for Quantifying Nucleic Acid Hybridization.
Biomacromolecules.
1133-1138.
2010
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Mechanisms by Which Human DNA Primase Chooses To Polymerize a Nucleoside Triphosphate.
Biochemistry.
727-735.
2010
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Incorporation of the Fluorescent Ribonucleotide Analogue tCTP by T7 RNA Polymerase.
Analytical Chemistry.
1082-1089.
2010
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Nucleotide Analogues as Probes for DNA and RNA Polymerases..
Current Protocols in Chemical Biology.
111-124.
2010
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Herpes Simplex Virus-1 DNA Primase: A Remarkably Inaccurate yet Selective Polymerase.
Biochemistry.
10866-10881.
2009
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Herpes Simplex Virus-1 Helicase-Primase: Roles of Each Subunit in DNA Binding and Phosphodiester Bond Formation.
Biochemistry.
10199-10207.
2009
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High Density Labeling of Polymerase Chain Reaction Products with the Fluorescent Base Analogue tCo.
Analytical Chemistry.
9079-9085.
2009
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Interaction of Human DNA Polymerase alpha and DNA Polymerase I from Bacillus stearothermophilus with Hypoxanthine and 8-Oxoguanine Nucleotides.
Biochemistry.
8271-8278.
2009
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Ambivalent Incorporation of the Fluorescent Cytosine Analogues tC and tCo by Human DNA Polymerase alpha and Klenow Fragment.
Biochemistry.
7547-7555.
2009
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Introduction to Cancer Chemotherapeutics.
Chemical Reviews.
2859-2861.
2009
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Discrimination between Right and Wrong Purine dNTPs by DNA Polymerase I from Bacillus stearothermophilus.
Biochemistry.
4633-4641.
2009
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Identifying the Features of Purine dNTPs that Allow Accurate and Efficient DNA Replication by Herpes Simplex Virus I DNA Polymerase.
Biochemistry.
3554-3564.
2009
- Herpes simplex virus-1 DNA primase: A remarkably inaccurate yet selective polymerase. ACS National Meeting Book of Abstracts. 535-535. 2009
- Role of the 2-amino group of purines during dNTP polymerization by human DNA polymerase alpha. ACS National Meeting Book of Abstracts. 528-528. 2009
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Initiation of New DNA Strands by the Herpes Simplex Virus-1 Primase-Helicase Complex and Either Herpes DNA Polymerase or Human DNA Polymerase alpha.
Journal of Biological Chemistry.
1523-1532.
2009
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Role of the 2-Amino Group of Purines during dNTP Polymerization by Human DNA Polymerase alpha.
Biochemistry.
180-189.
2009
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Interaction of herpes primase with the sugar of a NTP.
Biochemistry.
8977-8984.
2008
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Detection of adamantane-resistant influenza on a microarray.
Journal of Clinical Virology.
117-123.
2008
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Evaluation of whip with historic subtype H1N1 influenza A viruses, including the 1918 "Spanish flu" strain.
Journal of Clinical Microbiology.
3807-3810.
2007
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Comparison of the MChip to viral culture, reverse transcription-PCR, and the QuickVue influenza A plus B test for rapid diagnosis of influenza.
Journal of Clinical Microbiology.
1234-1237.
2007
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Real-time quantification of RNA polymerase activity using a "broken beacon".
Analytical Biochemistry.
213-220.
2007
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Diagnostic microarray for influenza B viruses.
Analytical Chemistry.
2084-2090.
2007
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Human DNA polymerase alpha uses a combination of positive and negative selectivity to polymerize purine dNTPs with high fidelity.
Biochemistry.
448-460.
2007
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Identification of A/H5N1 influenza viruses using a single gene diagnostic microarray.
Analytical Chemistry.
378-384.
2007
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MChip: A tool for influenza surveillance.
Analytical Chemistry.
7610-7615.
2006
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A mass spectrometry-based approach for identifying novel DNA polymerase substrates from a pool of dNTP analogues.
Nucleic Acids Research.
2006
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Experimental evaluation of the FluChip diagnostic microarray for influenza virus surveillance.
Journal of Clinical Microbiology.
2863-2871.
2006
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Intramolecular and intermolecular uridylylation by poliovirus RNA-dependent RNA polymerase.
Journal of Virology.
7405-7415.
2006
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Robust sequence selection method used to develop the FluChip diagnostic microarray for influenza virus.
Journal of Clinical Microbiology.
2857-2862.
2006
- Solid-phase synthesis of nucleosides and nucleotides. ACS National Meeting Book of Abstracts. 2006
- Mechanisms by which DNA and RNA polymerases discriminate between right and wrong (d)NTPs. Federation proceedings. A512-A513. 2006
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Introduction: DNA damage and repair.
Chemical Reviews.
213-214.
2006
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ConFind: a robust tool for conserved sequence identification.
Computer applications in the biosciences : CABIOS.
4420-4422.
2005
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Optimization of fragmentation conditions for microarray analysis of viral RNA.
Analytical Biochemistry.
316-323.
2005
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Herpes simplex virus 1 primase employs Watson-Crick hydrogen bonding to identify cognate nucleoside triphosphates.
Biochemistry.
15585-15593.
2005
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Herpes simplex virus 1 primase employs watson-crick hydrogen bonding to identify cognate nucleoside triphosphates..
Biochemistry.
15585-15593.
2005
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Exploration of factors driving incorporation of unnatural dNTPS into DNA by Klenow fragment (DNA polymerase I) and DNA polymerase alpha.
Nucleic Acids Research.
2620-2628.
2005
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Polymerization of the triphosphates of AraC, 2 ',2 '-difluorodeoxycytidine (dFdC) and OSI-7836 (T-araC) by human DNA polymerase alpha and DNA primase.
Biochemical Pharmacology.
2337-2346.
2004
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Human DNA primase uses Watson-Crick hydrogen bonds to distinguish between correct and incorrect nucleoside triphosphates.
Biochemistry.
12367-12374.
2004
- Incorporation versus elongation of nucleotide analogs by DNA polymerases: Orthogonal selection mechanisms?.. ACS National Meeting Book of Abstracts. U175-U175. 2004
- Nucleotide polymerases have evolved multiple mechanisms to differentiate right and wrong (d)NTPS.. ACS National Meeting Book of Abstracts. U304-U304. 2004
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Herpes simplex virus-1 primase: A polymerase with extraordinarily low fidelity.
Biochemistry.
9084-9091.
2004
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Herpes simplex virus-1 primase: a polymerase with extraordinarily low fidelity..
Biochemistry.
9084-9091.
2004
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Mechanism of primer synthesis by the herpes simplex virus 1 helicase-primase.
Biochemistry.
1754-1762.
2004
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Facile polymerization of dNTPs bearing unnatural base analogues by DNA polymerase alpha and Klenow fragment (DNA polymerase I).
Biochemistry.
10472-10481.
2003
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Facile polymerization of dNTPs bearing unnatural base analogues by DNA polymerase alpha and Klenow fragment (DNA polymerase I)..
Biochemistry.
10472-10481.
2003
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Key role of template sequence for primer synthesis by the herpes simplex virus 1 helicase-primase.
Biochemistry.
14569-14579.
2002
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Synthesis of nucleotide analogues that potently and selectively inhibit human DNA primase.
Biochemistry.
14066-14075.
2002
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The p58 subunit of human DNA primase is important for primer initiation, elongation, and counting.
Biochemistry.
4891-4900.
2002
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Inhibition of CMP-sialic acid transport into Golgi vesicles by nucleoside monophosphates.
Biochemistry.
14260-14267.
2001
- Kinetic analysis of the CMP-sialic acid transporter of the Golgi apparatus.. Glycobiology. 919-919. 2001
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Eukaryotic DNA primase.
Trends in Biochemical Sciences.
572-576.
2000
- Investigation of the binding and substrate specificity of the CMP-sialic acid transporter of the Golgi apparatus. Glycobiology. 1080-1081. 2000
- 3 '-azidothymidine potently inhibits the biosynthesis of highly branched N-linked oligosaccharides and poly-N-acetyllactosamine chains in cells. Journal of Biological Chemistry. 26812-26820. 2000
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Polymerization of 2 '-fluoro-and 2 '-O-methyl-dNTPs by human DNA polymerase alpha, polymerase gamma, and primase.
Biochemical Pharmacology.
1045-1052.
2000
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Over four hundred million characters served: 99 volumes, 2567 articles, 85623 pages, and moro than 85 million words.
Chemical Reviews.
1-6.
2000
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Abasic template lesions are strong chain terminators for DNA primase but not for DNA polymerase alpha during the synthesis of new DNA strands.
Biochemistry.
12908-12914.
1999
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Interactions of DNA with human DNA primase monitored with photoactivatable cross-linking agents: Implications for the role of the p58 subunit.
Biochemistry.
12899-12907.
1999
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Human DNA primase: Anion inhibition, manganese stimulation, and their effects on in vitro start-site selection.
Biochemistry.
10126-10134.
1999
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Arg304 of human DNA primase is a key contributor to catalysis and NTP binding: Primase and the family X polymerases share significant sequence homology.
Biochemistry.
7727-7736.
1999
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3 '-azidothymidine significantly alters glycosphingolipid synthesis in melanoma cells and decreases the shedding of gangliosides.
Glycoconjugate Journal.
237-245.
1999
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Eucaryotic DNA primase does not prefer to synthesize primers at pyrimidine rich DNA sequences when nucleoside triphosphates are present at concentrations found in whole cells.
Biochemistry.
6725-6731.
1997
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Inhibition of UDP-N-acetylglucosamine import into Golgi membranes by nucleoside monophosphates.
Journal of medicinal and pharmaceutical chemistry.
2894-2899.
1996
- Isotopic assays of viral polymerases and related proteins. Methods in Enzymology. 241-257. 1996
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INTERACTIONS OF CALF THYMUS DNA-POLYMERASE-ALPHA WITH PRIMER/TEMPLATES.
Nucleic Acids Research.
4109-4115.
1995
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3'-AZIDOTHYMIDINE (ZIDOVUDINE) INHIBITS GLYCOSYLATION AND DRAMATICALLY ALTERS GLYCOSPHINGOLIPID SYNTHESIS IN WHOLE CELLS AT CLINICALLY RELEVANT CONCENTRATIONS.
Journal of Biological Chemistry.
22836-22841.
1995
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INACTIVATION OF DNA-POLYMERASE ALPHA-PRIMASE BY ACROLEIN - LOSS OF ACTIVITY DEPENDS ON THE DNA SUBSTRATE.
Biochemical and Biophysical Research Communications.
971-977.
1995
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ARABINOFURANOSYL NUCLEOTIDES ARE NOT CHAIN-TERMINATORS DURING INITIATION OF NEW STRANDS OF DNA BY DNA-POLYMERASE ALPHA-PRIMASE.
Biochemistry.
11198-11203.
1995
- 3'-AZIDO-3'-DEOXYTHYMIDINE MONOPHOSOPHATE (AZTMP) POTENTLY INHIBITS GOLGI SPECIFIC GLYCOSYLATION REACTIONS. Federation proceedings. A1361-A1361. 1995
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ACYCLIC GUANOSINE ANALOGS INHIBIT DNA POLYMERASE-ALPHA, POLYMERASE-DELTA, POLYMERASE-EPSILON WITH VERY DIFFERENT POTENCIES AND HAVE UNIQUE MECHANISMS OF ACTION.
Biochemistry.
2504-2510.
1995
- MISINCORPORATION OF NUCLEOTIDES BY CALF THYMUS DNA PRIMASE AND ELONGATION OF PRIMERS CONTAINING MULTIPLE NONCOGNATE NUCLEOTIDES BY DNA-POLYMERASE-ALPHA. Journal of Biological Chemistry. 19225-19231. 1994
- 3'-AZIDO-3'-DEOXYTHYMIDINE POTENTLY INHIBITS PROTEIN GLYCOSYLATION - A NOVEL MECHANISM FOR AZT CYTOTOXICITY. Journal of Biological Chemistry. 14355-14358. 1994
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CALF THYMUS DNA-POLYMERASE ALPHA-PRIMASE - COMMUNICATION AND PRIMER-TEMPLATE MOVEMENT BETWEEN THE 2 ACTIVE-SITES.
Biochemistry.
2247-2254.
1994
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DNA POLYMERASE-EPSILON - APHIDICOLIN INHIBITION AND THE RELATIONSHIP BETWEEN POLYMERASE AND EXONUCLEASE ACTIVITY.
Biochemistry.
8568-8574.
1993
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MECHANISM OF CALF THYMUS DNA PRIMASE - SLOW INITIATION, RAPID POLYMERIZATION, AND INTELLIGENT TERMINATION.
Biochemistry.
3027-3037.
1993
- ANALYSIS OF LAGGING STRAND DNA-SYNTHESIS IN ISOLATED-NUCLEI. Cell regulation. A135-A135. 1992
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INHIBITION OF DNA PRIMASE AND POLYMERASE-ALPHA BY ARABINOFURANOSYLNUCLEOSIDE TRIPHOSPHATES AND RELATED-COMPOUNDS.
Biochemistry.
4720-4728.
1992
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Mechanism of DNA polymerase .alpha. inhibition by aphidicolin.
Biochemistry.
8590-8597.
1991
- INHIBITION OF DNA PRIMASE BY 9-BETA-D-ARABINOFURANOSYL-ADENOSINE-TRIPHOSPHATE. Federation proceedings. A436-A436. 1991
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MECHANISM OF DNA-REPLICATION FIDELITY FOR 3 MUTANTS OF DNA-POLYMERASE-I - KLENOW FRAGMENT KF(EXO+), KF(POLA5), AND KF(EXO-).
Biochemistry.
1441-1448.
1991
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INHIBITION OF DNA PRIMASE BY 9-BETA-D-ARABINOFURANOSYLADENOSINE TRIPHOSPHATE.
Biochemistry.
797-803.
1991
- DNA PRIMASE - PROCESSIVITY AND THE PRIMASE TO POLYMERASE ALPHA-ACTIVITY SWITCH. Journal of Biological Chemistry. 16158-16165. 1990
- THE MECHANISM OF KLENOW FRAGMENT MISINCORPORATION. ACS National Meeting Book of Abstracts. 87-BIOL. 1990
- THE MECHANISM OF KLENOW FRAGMENT MISINCORPORATION. Biochemistry. 2195-2195. 1990
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Kinetic mechanism of DNA polymerase I (Klenow).
Biochemistry.
8410-8417.
1987
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Iron-sulfur centers in lactyl-CoA dehydratase.
Biochemistry.
7301-7307.
1986
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Synthesis of Small-Molecule/DNA Hybrids through On-Bead Amide-Coupling Approach.
Journal of Organic Chemistry.
10803-10811.
2017
Teaching
courses taught
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BCHM 4400 - Core Concepts in Physical Chemistry for Biochemists
Primary Instructor - Fall 2018
Introduces thermodynamics, kinetics and spectroscopy, emphasizing macromolecule and biochemical applications. Includes thermodynamics, chemical and physical equilibriums, solution chemistry, rates of chemical and biochemical reactions, chemical bonds and principles and selected examples of spectroscopies applied to biological systems. Department enforced prerequisite or corequisite: PHYS 1120 or PHYS 2020. Formerly CHEM 4411. Same as BCHM 5400 and CHEM 4511. -
BCHM 5400 - Core Concepts in Physical Chemistry for Biochemists
Primary Instructor - Fall 2018
Introduces thermodynamics, kinetics and spectroscopy, emphasizing macromolecule and biochemical applications. Includes thermodynamics, chemical and physical equilibriums, solution chemistry, rates of chemical and biochemical reactions, chemical bonds and principles and selected examples of spectroscopies applied to biological systems. Formerly CHEM 5411. Same as BCHM 4400 and CHEM 4511. -
BCHM 6901 - Research in Biochemistry
Primary Instructor - Fall 2019 / Spring 2020
Research in Biochemistry -
CHEM 6901 - Research in Chemistry
Primary Instructor - Spring 2018 / Summer 2018 / Fall 2018 / Spring 2019 / Summer 2019 / Spring 2020
May be repeated up to 15 total credit hours.
Background
education and training
- Ph.D., Brandeis University 1986
- B.A., Cornell University 1979
awards and honors
International Activities
global connections related to teaching and scholarly work (in recent years)
- Czech Republic Country
- eastern Europe Transnational Region