个人简介

B.A. (1980): New York University B.S. (1989): SUNY at Purchase M.A. (1990) : Columbia University M.Phil. (1993) : Columbia University Ph.D. (1994) : Columbia University NIH Fellowship (1994-1997) : California Institute of Technology 2010-present Professor of Chemistry, Georgia State University 2003-2010 Associate Professor of Chemistry, Georgia State University 1997-2003 Assistant Professor, Department of Chemistry, Georgia State University. 1994-1997 NIH Postdoctoral Fellow, Department of Chemistry, California Institute of Technology 1990-1994 Doctoral Research, Department of Chemistry, Columbia University

研究领域

Cleavage of Peptides and Proteins by Metal Complexes Reagents which mediate the selective cleavage of peptides and proteins have become increasingly important to the fields of chemistry and biology for protein structural analyses. However, the extreme stability of the peptide amide bond has placed severe limits on the number of reagents available and there is a great need for new cleavage strategies. Our research is focused on the development of combinatorial methods for the rapid discovery of new metal ions and complexes for peptide cleavage. A positional scanning peptide library consisting of 8,000 discrete tripeptides within 60 sub-libraries will be synthesized by solid phase methods. Modification of cleaved peptides with a highly sensitive fluorophore will permit the rapid analysis of all 60 sub-libraries and rapid screening of a broad range of metal ions and complexes. Using positional scanning, we will identify both amino acid sequences that are cleaved by metals and optimal metal reagents for peptide cleavage. We anticipate that these studies will lead to the discovery of new and unexpected chemistry that will enable us to rationally design second generation complexes with enhanced cleavage efficiencies. The 5-HT Transporter in Antidepressant Drug Resistance Major depression is a severe and disabling mood disorder for which there is no cure. Although tricyclic antidepressant drugs and selective serotonin reuptake inhibitors (SSRI’s) which bind to or block the serotonin transporter (5-HTT, SERT) have been successful in the treatment of major depression, a subset of patients (~20% – 30%) is nonresponsive to drug therapy. The effect of poor treatment outcome contributes substantially to the morbidity and mortality associated with major depression. Unfortunately, there are no truly reliable clinical predictors of response to antidepressants and there is no clear understanding of mechanisms that underlie drug resistance. We are currently employing the polymerase chain reaction (PCR) as a screen for polymorphisms in coding and noncoding regions of the 5-HTT gene of refractory patients in order to determine if the serotonin transporter plays a pathogenic role in the phenomenon of antidepressant drug resistance. By identifying amino acid residues that are critical for drug/transporter interactions, these studies may provide structural leads for the development of potentially more effective drugs.

Our research explores the chemical properties of biomolecules by an interdisciplinary approach that extends into the fields of inorganic chemistry, organic chemistry, and molecular biology.

近期论文

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Grant, K.B.,* Terry, C.A., Gude, L., Fernández, M.-J., & Lorente, A.* “Synthesis and DNA Photocleavage by a Pyridine-Linked Bis-Acridine Chromophore in the Presence of Copper(II): Ionic Strength Effects.” (2011) Bioorganic & Medicinal Chemistry Letters, 21, 1047-1051. Kassai, M., Teopipithaporn, R., & Grant, K.B.* “Hydrolysis of Phosphatidylcholine by Cerium(IV) Releases Significant Amounts of Choline and Inorganic Phosphate at Lysosomal pH.” (2011) Journal of Inorganic Biochemistry, 105, 215-223. Wilson, B., Fernández, M.-J., Lorente, A.,* & Grant, K.B.* “Synthesis and DNA Interactions of a Bis-Phenothiazinium Photosensitizer.” (2008) Organic & Biomolecular Chemistry, 6, 4026 – 4035. (Selected for inclusion in the Royal Society of Chemistry virtual journal Chemical Biology, Issue 12, 2008.) Wilson, B., Fernández, M.-J., Lorente, A.,* & Grant, K.B.* ”Syntheses and DNA Photocleavage by Mono– and Bis-phenothiazinium-piperazinexylene Intercalators” (2008) Tetrahedron, 64, 3429-3436. Cepeda, S.S., & Grant, K.B.* ”Hydrolysis of Insulin Chain B Using Zirconium(IV) at Neutral pH.” (2008) New Journal of Chemistry, 32, 388-391.