Background:

• Indiana University Outstanding Young Faculty Award, 1993-94
• American Cancer Society Junior Faculty Research Award, 1994-96
• Camille Dreyfus Teacher-Scholar Award, 1994
• Alfred P. Sloan Fellow, 1995-97
• Gill Fellow, College of Arts and Sciences, Indiana University, 1997-2001

Our group concentrates on the development of methodologies to address problems of biochemical and biomedical interest. For example, the molecule shown below, an analogue of a naturally occurring oligonucleotide, holds promise for the treatment of viral diseases such as AIDS, for control of the unwanted expression of genetic information such as occurs in cancer cells, and for enhancing our understanding of the physical characteristics of nucleic acids and their interaction with proteins. We are also developing methodology for the synthesis and design of other kinds of unnatural nucleic acids, as well as saccharides, lipids, and a variety of enzyme inhibitors that are of potential therapeutic value.

The study of enzyme mechanisms by use of isotope effects, stereochemical probes, and artificial substrate analogues forms the basis for another area of research in our group. The development of functional group equivalents for the enhanced molecular recognition of protein ligands is an extension of our interest in the application of physical organic chemistry to the solution of biochemical problems. The use of such enhanced protein ligand interactions is being actively pursued for the development of antiviral agents and enzyme inhibitors.

We have also developed strategies for the potent and specific inhibitors of enzymes involved in signal transduction. Such advances should greatly facilitate the study of cell transformation and metabolism.

Selected Publications:

"4-(Fluoromethyl)phenyl phosphate acts as a mechanism-based inhibitor of calcineurin," with T. L. Born, J. K. Myers, and F. Rusnak. J. Biol. Chem., 270, 25651 (1995).

"Molecular recognition in biological systems: phosphate esters vs sulfate esters and the mechanism of action of steroid sulfatases," with C. J. Anderson and L. J. H. Lucas. J. Am. Chem. Soc., 117, 3889 (1995).

"A new method for the phosphorylation of alcohols and phenols," with J. K. Stowell. Tetrahedron Lett., 36, 1825 (1995).

"Substituent effects on the mechanism-based inactivation of prostatic acid phosphatase," with J. K. Myers and J. D. Cohen. J. Am. Chem. Soc., 117, 11049 (1995).

"Mechanism-based inactivation of ribonuclease A," with J. K. Stowell, T. G. Kutateladze, and R. T. Raines. J. Org. Chem., 60, 6930 (1995).

"Charged with meaning: the structure and mechanism of phosphoprotein phosphatases," with W. P. Taylor. Chem. Biol., 2, 713 (1995).

"Quiescent affinity inactivators of protein tyrosine phosphatases," with W. P. Taylor and Z.-Y. Zhang. Bioorg. Med. Chem., 4, 1515 (1996).

"Resolution and determination of the enantiomeric purity and absolute configurations of alpha-aryl-alpha-hydroxymethanephosphonates," with W. Pirkle, H. L. J. Brice, and J. Roestamadji. Tetrahedron: Asymmetry, 7, 2173 (1996).

"A new protecting group for the synthesis of complex sulfonates," with M. Xie. Tetrahedron Lett., 37, 4443 (1996).

"The road less traveled: taming phosphatases," with J. K. Myers, B. Stec, K. M. Holtz, and E. R. Kantrowitz. Chem. Biol., 4, 489 (1997).

"Chemistry and enzymology of phosphatases," with W. Taylor. Comp. Nat. Prod. Chem., 5, 139 (1999).

"Facile preparation of nucleoside-5`-carboxylic acids," with J. B. Epp. J. Org. Chem., 64, 293 (1999).