Research in Karver's lab broadly focuses
on the chemical biology, bioorganic and medicinal chemistry of enzymes
implicated in disease states. The lab uses synthetic organic chemistry
as well as biochemical techniques to study biological systems of
therapeutic interest.
One area of interest focuses on the
development of probes to study caspase-1, a cysteine protease involved
in autoimmune diseases and inflammatory cancers. Our current assay to
study this enzyme uses a peptide-based fluorescent substrate with
relatively slow kinetic properties. One project seeks to develop new
small molecule fluorescent substrates with improved rates of reaction
with caspase-1. A second project involves the synthesis of new
inhibitors of caspase-1 based on known inhibitors in the literature as
well as ones discovered in our lab.
Another project involves the
synthesis and analysis of binding properties of inhibitors of histone
deacetylases (HDACs). HDACs are targets of anti-cancer therapeutics that
contain a catalytic Zn(II) in the active site. Upon synthesis of
inhibitors, the binding energetics of the interaction of the inhibitor
with the catalytic Zn(II) are determined by Isothermal Titration
Calorimetry in collaboration with Drs. Lihua Jin and Kyle Grice in the
chemistry department.
Margaret Kawarski and Caitlin E. Karver “Lazaroids U83836E and U74389G are Potent, Time-dependent Inhibitors of Caspase-1” ChemMedChem manuscript in revisions
Erin K. Gallagher, Caitlin E. Karver, Stephanie S.
Lyngaas and Lihua Jin “Binding energetics of the histone deacetylase
inhibitor suberoylanilide hydroxamic acid with zinc(II) and cobalt(II)” manuscript in preparation
Caitlin E. Karver, Eric S. Molina, Erin T. Economos,
Jonathan C. Fuentes, Socrates M. Kaitson, Samuel Kogan, Gemma Levi,
Jill K. Marcus, Stacey Mei, Sean C. Reinsalu, Kathryn Rico, Magdalena M.
Zuzek, and Gregory B. Kharas “Novel Copolymers of Styrene. 12. Halogen
Ring-Substituted Methyl 2-Cyano-3-Phenyl-2-Propenoates” Journal of Macromolecular Science Part A: Pure and Applied Chemistry 2014, 51, 101-105
Stephanie M. Sanford, Divya Krishnamurthy, Caitlin E. Karver,
Logan Walker, Chen-Ting Ma, Thomase D.Y. Chung, Eduard Sergienko,
Nunzio Bottini, and Amy M. Barrios “pCAP-based peptide substrates: the
new tool in the box of tyrosine phosphatase assays” Methods, 2014, 65, 165-174
Gautam Patel, Caitlin E. Karver, Ranjan Behera,
Paul Guyett, Peter Edwards, Norma E. Roncal, Richard J. Sciotti, Kojo
Mensa-Wilmot, and Michael P. Pollastri “Kinase scaffold repurposing for
neglected disease drug discovery: A structure-activity relationship
study of lapatinib analogs as anti-trypanosomal agents” Journal of Medicinal Chemistry, 2013, 56, 3820–3832
Rosario Diaz-Gonzalez, F. Matthew Kuhlmann, Cristina Galan-Rodriguez, Luciana Madeira da Silva, Manuel Saldivia, Caitlin E. Karver,
Ana Rodriguez, Stephen M. Beverley, Miguel Navarro, Michael P.
Pollastri “The Susceptibility of Trypanosomatid Pathogens to PI3/mTOR
Kinase Inhibitors Affords a New Opportunity for Drug Repurposing” PLoS Neglected Tropical Diseases, 2011, 5, e1297
Caitlin E. Karver, Vanessa F. Ahmed, and Amy M.
Barrios “Oxidative Inactivation of the Lymphoid Tyrosine Phosphatase
Mediated by Both General and Active Site Directed NO Donors” Bioorganic and Medicinal Chemistry Letters, 2011, 21, 285-287
Caitlin E. Hubbard, Amy M. Barrios. “A Highly
Efficient Route to Enantiomerically Pure L-N-Bz-Pmp(t-Bu)2-OH and
incorporation into a peptide-based protein tyrosine phosphatase
inhibitor” Bioorganic and Medicinal Chemistry Letters, 2008, 18, 679-681