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Activities & Awards
Japan Soc. for the Promotion of Science Research
Fellow, 1989-90
NSF Creativity Award, 1993-95
NSF Career Advancement Award, 1993-94
Bioorganic & Natural Products Study Section, NIH, 1990-94
Robert W. Parry Teaching Award, 2002
ACS Utah Award, 2000
Assoc. Editor, Organic Letters, 1999
Senior Editor, Journal of Organic Chemistry, 2001-present
Research
Interests:
The heterocyclic bases of nucleic acids are rich targets for both
toxins that damage DNA and drugs that interact with DNA and RNA. Our laboratory
investigates several different aspects of nucleic acid chemistry ranging
from base recognition by various probes to base reactions with oxidizing
and alkylating agents. Tools used in our lab include:
- nucleic
acid, peptide and ligand synthesis
- organic
reaction mechanisms
- bioinorganic
methods of studying metal ion complexes
- gel electrophoresis,
PCR and polymerase assays
- ESI-MS
- cellular
studies of gene transfection.
Chemistry and Biochemistry
of Guanine Oxidation.
Many health problems ranging from cancer to aging stem from oxidative
damage to DNA. Within DNA, guanine is the site most susceptible to oxidation.
We are currently investigating the mechanistic pathways of one-electron
oxidation of G to 8-oxoG and leading on to guanidinohydantoin and spiroiminodihydantoin
products. Both the misinsertion of bases opposite new lesions by polymerases
and their repair by DNA repair enzymes (in collaboration with Sheila David)
are under investigation. In RNA, oxidation of Gs forms the basis of a
structural probe of this residue. Recent studies have also revealed special
reactivity adjacent
G·U wobble pairs.
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Steroidal Polyamines as Transfection Agents:
Cationic lipids are of interest as gene transfection agents since
they bind well to DNA and aid in cell permeation. We are in the process
of developing new cationic polymers with appended steroid hormones for
cell targeting.
Metallopeptides and DNA: Certain peptide motifs including CXH
and the N-terminal sequence XXH are good binding sites for nickel(II)
and copper(II). When incorporated into a DNA-binding domain of a peptide
or protein, these redox-active metal complexes lead to DNA cleavage or
cross-linking. A new bioconjugate, the Sal-XH ligand, has been designed
as a peptide-DNA (or RNA) cross-linking agent in order to investigate
nucleic acid binding sites of peptide antibiotics.
Selected Publications
- M. E. Hosford, J. G. Muller, and C. J. Burrows, "Spermine participates in oxidative damage of guanosine and 8-oxoguanosine leading to deoxyribosylurea formation," J. Am. Chem. Soc . 2004 , 126 , 0000.
- S. Choi, J. G. Muller, C. J. Burrows, et al., "Mechanism of 2-e- oxidation of 5-dGMP by a Pt(IV) complex,"J. Am. Chem. Soc . 2004 , 126 , 591.
- Y. Ye, J. G. Muller, W. Luo, C. L. Mayne, A. J. Shallop, R. A. Jones, and C. J. Burrows, "Formation of 13C-, 15N- and 18O-labeled guanidinohydantoin from guanosine oxidation with singlet oxygen. Implications for structure and mechanism," J. Am. Chem. Soc . 2003 , 125 , 13926.
- O. Kornyushyna and C. J. Burrows, "Effect of the oxidized lesions Sp and Gh on proofreading by Klenow fragment," Biochemistry 2003 , 42, 13008.
- W. Luo, J.G. Muller, and C.J. Burrows, "The pH-dependent role of superoxide in riboflavin-catalyzed photooxidation of 8-oxo-7,8-dihydroguanosine," Org . Lett . 2001 , 3 , 2801-2804.
- W. Luo, J. G. Muller, E. Rachlin, and C. J. Burrows, "Characterization of spiroiminodihydantoin as a product of 7,8-dihydro-8-oxoguanosine oxidation," Org. Lett. 2000 , 2 , 613-616.
- R. P. Hickerson, C. L. Chepanoske, S. D. Williams, S. S. David, and C. J. Burrows, "Mechanism-based DNA-protein cross-linking of MutY via oxidation of 8-oxoguanosine," J. Am. Chem. Soc. 1999 , 121 , 9901-9902.
- R. P. Hickerson, F. Prat, J. G. Muller, C. S. Foote, and C. J. Burrows, "Sequence and stacking dependence of 8-oxoguanine oxidation: Comparison of one-electron vs. singlet oxygen mechanisms," J. Am. Chem. Soc. 1999 , 121 , 9423-9428.
- J. Stemmler and C. J. Burrows, "The Sal-XH motif for metal-mediated oxidative DNA-peptide cross-linking," J. Am. Chem. Soc . 1999 , 121 , 6956-6957.
- C.J. Burrows and J.G. Muller, "Oxidative nucleobase modifications leading to strand scission," Chem. Rev. 1998 , 98, 1109-1152.
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