Lindsay R. Comstock-Ferguson
B.S., 2000, Northern Arizona University
Ph.D. (Pharmaceutical Sciences), University of Wisconsin-Madison
Postdoc (Biomolecular Chemistry, J.M. Denu), University of Wisconsin-Madison
Office: Salem 16A
Phone: (336) 758-5514
Description of Research
Research in our laboratory lies at the chemistry-biology interface and seeks to gain a deeper understanding of the role of post-translational modifications in the dynamic regulation of cellular function and how alterations in these modification states correlate to disease. The combination of organic chemistry, biochemistry, and molecular biology is utilized in developing small-molecule tools to not only identify where substrates are modified, but to investigate the physiological effect of such modifications in vivo. Specifically, cofactor mimics of S-adenosyl-L-methionine and adenosine triphosphate bearing reactive functionalities serve as substrates for cellular methyltransferases and kinases, respectively, to generate easily-detected biological complexes. Ultimately, the long-term value of such agents to serve as biochemical tools will allow us to begin understanding the underlying chemical driving forces which induce and alter biologically important processes and disease through post-translational modifications.
Ramadan, M, Bremner-Hay, NK, Carlson, S, Comstock, LR. Synthesis and evaluation of N6-substituted azide- and alkyne-bearing N-mustard analogs of S-adenosyl-L-methionine. Tetrahedron. 2014;70:5291-5297.
Du, Y, Hendrick, CE, Frye, KS, Comstock, LR. Fluorescent DNA labeling by N-mustard analogs of S-adenosyl-L-methionine. ChemBioChem. 2012;13:2225-2232.
Mai, V, Comstock, LR. Synthesis of an azide-bearing N-mustard analog of S-adenosyl-L-methionine. J Org Chem. 2011;76:10319-10324.
Comstock, LR, Rajski, SR. Methyltransferase-directed DNA strand scission. J Am Chem Soc 2005;127:14136-14137.
Comstock, LR, Rajski, SR. Conversion of DNA methyltransferases into azidonucleosidyl transferases via synthetic cofactors. Nucleic Acids Res 2005;33:1644-1652.