|Kathryn Betty Grant|
Graduate Biochemistry Advisor
Biochemistry, Bioinorganic Chemistry
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
Dr. Kathryn Betty Grant
Department of Chemistry
Georgia State University
P.O. Box 3965
Atlanta, Georgia 30302-3965
Department Office Phone: 404-413-5500
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.
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.
In the figure above, a positional scanning peptide library composed of eight tripeptides is screened with metal ions that promote oxidative peptide cleavage. Relative fluorescence of library samples treated with (i) vanadium(V)/light and (ii) copper(II)/ ascorbate reveals that KPG is the most reactive tripeptide motif.
(The eight tripeptides are divided into two samples within each of three sub-libraries, based on the identity of the spatially addressed amino acid "O", which alternates between Lys and Gly in Sub-library 1, Pro and Gly in Sub-library 2, and His and Gly in Sub-library 3.)
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.
The structure of serotonin (5-HT) and a schematic model of the serotonin transporter. Antidepressants bind to 5-HTT and exert their effect by competitively blocking serotonin reuptake into presynaptic serotonergic neurons.
|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, with Professor Peter B. Dervan.|
|Research: sequence specific cleavage of duplex DNA by major groove-binding oligonucleotide and minor groove-binding polyamide conjugates.|
|1990-1994||Doctoral Research, Department of Chemistry, Columbia University, with Professor Koji Nakanishi; Visiting Student at the Johns Hopkins University School of Medicine, with Professor Jeremy Nathans.|
|Research: vanadium-tunichrome complexation and redox chemistries; cloning and expression of goldfish opsin sequences.|
|2007-2011||NSF GRANT (Georgia State)|
|2000-2006||NSF CAREER Award (Georgia State)|
|1998-2000||Petroleum Research Fund, Type G Grant (Georgia State)|
|1994-1997||NIH Postdoctoral Fellowship (CalTech)|
|1994||Pegram Award for Outstanding Research (Columbia University)|
|1992-1993||NIH Training Fellowship (Columbia University)|
|1991-1992||Eli Lilly and Company Fellowship (Columbia University)|
|1991||J. Malcolm Miller Award for Distinguished Teaching (Columbia University)|
|1989||Irene Goldring Award for Outstanding Performance in Science (SUNY at Purchase)|
|1989||B.S. summa cum laude in Chemistry (SUNY at Purchase)|
|1988-1989||Technicon Research Fellowship (SUNY at Purchase)|
Center for Metalloenzyme Studies, University of Georgia, Adjunct Faculty Member
M.D./Ph.D. Program, Medical College of Georgia, Adjunct Faculty Member