Casey J. Krusemark
Ph.D. Biochemistry, 2007, University of Wisconsin--Madison (under Peter Belshaw)
B.S. Chemistry, B.S. Crop Science, 2001, University of Illinois--Urbana-Champaign (under Jack Widholm)
Our work centers on two nascent technologies that not only borrow from the structure of nature’s bioactive molecules but also from nature's approaches to synthesize molecules and assess them for function. These two approaches enable the transduction of synthetic molecule structural and/or functional information into DNA sequences. Application of the powerful tools available to read, write, and manipulate DNA-encoded information provides a number of advantages over traditional approaches, such as throughput, sensitivity, and sample multiplexing. In the first approach, we employ DNA-programmed combinatorial chemistry for the construction of DNA-encoded small molecule libraries, which can be collectively assayed by in vitro evolution. Our work in this area involves development of novel libraries and selection strategies for discovery of protein-protein interaction inhibitors, with a particular focus on peptidomimetics for protein substrate-competitive kinase inhibition. In the second area, we have developed an evolution-inspired assay approach to detect sample stimuli using DNA-linked molecules as probes. We have developed DNA-encoded probes for detection of several enzymatic activities, as well as synthetic ligand binding, which allow activity detection through DNA sequence analysis. We work to apply this approach in proteomic activity profiling and in screening of small molecules for enzyme inhibition.
MCMP 205 Organic Chemistry II
MCMP 208 Biochemistry for Pharmaceutical Sciences I
NINDS R21 (1NS101535) (02/01/2017-01/31-2019)
(PIs: Hockerman, GH and Krusemark, CJ) Differential modulation of Cav1.2 and Cav1.3)
Denton, K. E., Wang, S., Gignac, M. C., Milosevich, N., Hof, F., Dykhuizen, E. C., Krusemark, C. J., "Robustness of In Vitro Selection Assays of DNA-encoded Peptidomimetic Ligands to CBX7 and CBX8." SLAS Discovery, 2018, In press. DOI: 10.1177/2472555217750871
Kim, D., Jetson, R. R., Krusemark, C. J., "A DNA-assisted Immunoassay for Enzyme Activity via a DNA-linked, Activity-based Probe." Chem. Comm. 2017, 53, 9474-9477.
Denton, K. E., Krusemark, C. J., "Crosslinking of DNA-linked ligands to target proteins for enrichment from DNA-encoded libraries." Med. Chem. Comm. 2016, 7, 2020-2027.
Jetson, R. R., Krusemark, C. J. "Sensing Enzymatic Activity by Exposure and Selection of DNA-encoded Probes." Angewandte Chemie Int. Ed. 2016, 55, 9562-9566.
Krusemark, C. J., Tilmans, N. P., Brown, P. O., Harbury, P. B., "Directed Chemical Evolution with an Outsized Genetic Code." PLoS ONE 11(8) e0154765.
Tilmans, N. P., Krusemark, C. J., Harbury, P. B., “Expedient Synthesis of a Modular Phosphate Affinity Reagent.” Bioconj. Chem. 2010, 21, 1010-1013.
Frey, B. L., Ladror, D. T., Sondalle, S. B., Krusemark, C. J., Jue, A. L., Coon, J. J., Smith, L. M., “Chemical derivatization of peptide carboxyl groups for highly efficient electron transfer dissociation." J. Am. Soc. Mass Spectrom. 2013, 24, 1710-1721.
Krusemark, C. J., Frey, B. L., Belshaw, P. B., Smith, L. M., "Modifying the Charge State Distribution of Proteins in Electrospray Ionization Mass Spectrometry by Chemical Derivatization." J. Am. Soc. Mass Spectrom. 2009, 20, 1617-1625.
Krusemark, C. J., Ferguson, J. T., Wenger, C. D., Kelleher, N. L., Belshaw, P. J., "Global Amine and Acid Functional Group Modification of Proteins." Analytical Chemistry. 2008, 80, 713-720.
Krusemark, C. J. and Belshaw, P. J., "Covalent Labelling of Fusion Proteins in Live Cells via an Engineered Receptor-Ligand Pair." Organic and Biomolecular Chemistry. 2007, 5, 2201-2204.
Krusemark, C. J.*, Lamos, S. M.*, McGee, C. J., Scalf, M., Smith, L. M., Belshaw, P. J., "Mixed Isotope Photoaffinity Reagents for Identification of Small Molecule Targets by Mass Spectrometry." Angewandte Chemie Int. Ed. 2006, 45, 4329-4333. *Authors contributed equally.