Michael Best Assistant Professor Organic Chemistry Bio-organic, supramolecular, and medicinal chemistry B.S., Boston College (1997) Ph.D., The University of Texas at Austin (2002)
E-mail: mdbest@utk.edu 353 Buehler Hall   ·   Telephone: 865-974-8658 Representative publications   ·   Biographical sketch  ·   Group Web Page

Research

Dr. Best's research generally involves the design and synthesis of molecules that can be implemented for studies or applications pertaining to biological systems.

One aspect of this involves the study of cell-surface recognition events. Here, carbohydrates and lipids presented on the cell-surface act as binding sites for a range of species including proteins, pathogens, and viruses. Due to the involvement of these compounds in crucial cellular events, it is necessary to understand these interactions to provide approaches for therapeutic intervention. Synthetic organic chemistry provides access to well-defined analogs of these epitopes that can be used to develop a microscopic understanding of these recognition events.

The group is also interested in the development of chemical sensors for the detection of therapeutically relevant biomolecules. The traditional approach in this realm involves the design of a supramolecular receptor that can selectively bind a given analyte, allowing for quantification. We are developing novel strategies that allow for efficient development of high affinity sensors. Such structures can be applied to the detection of target analytes for the purpose of clinical diagnosis.

The research in the group entails the combination of traditional synthetic organic chemistry to obtain the target compounds, biochemistry techniques to study protein interactions, and analytical approaches for binding characterization. We interact with a range of collaborators to achieve these goals. While students generally focus on the areas that best fit their interests, they also obtain an interdisciplinary training, providing them with a wide range of skills and preparing them to be successful in whatever arena there ambitions may take them.

Representative publications

Carbohydrate microarray for profiling the antibodies interacting with Globo H tumor antigen. C.-Y. Huang, D.A. Thayer, A.Y. Chang, M.D. Best, J.A. Hoffman, S. Head, C.-H. Wong. Proc. Natl. Acad. Sci. U.S.A. 103, 15 (2006).

Dissection of the carbohydrate specificity of the broadly neutralizing anti-HIV-1 antibody 2G12. D.A. Calarese, H.-K. Lee, C.-Y. Huang, M.D. Best, R. Astronomo, R.L. Stanfield, H. Katinger, D. Burton, C.-H. Wong, I.A. Wilson. Proc. Natl. Acad. Sci. U.S.A. 102, 13372 (2005).

Tetrabutylammonium fluoride-assisted rapid N9-alkylation on purine ring: application to combinatorial reactions in microtiter plates for the discovery of potent sulfotransferase inhibitors in situ. A. Brik, C.-Y. Wu, M.D. Best, C.-H. Wong, Bioorg. Med. Chem. 13, 4622 (2005).

Covalent display of oligosaccharide arrays in microtiter plate. M.C. Bryan, F. Fazio, H.-K. Lee, C.-Y. Huang, A. Chang, M.D. Best, D.A. Calarese, O. Blixt, J.C. Paulson, D. Burton, I.A. Wilson, and C.-H. Wong, J. Am. Chem. Soc. 126, 8640 (2004).

Development of highly potent sulfotransferase inhibitors using multiple rounds of library formation to optimize linker length and binding group identities. M.D. Best, A. Brik, E. Chapman, L.V. Lee, W.-C. Cheng, and C.-H. Wong, ChemBioChem 5, 811 (2004).

Chemoenzymatic synthesis of oligosaccharides and glycoproteins. S.R. Hanson, M.D. Best, M.C. Bryan, and C.-H. Wong, Trends Biochem. Sci. 29, 656 (2004).

Sulfatases: structure, mechanism, biological activity, inhibition and synthetic utility. S.R. Hanson, M.D. Best, and C.-H. Wong, Angew. Chem. Int. Ed. 43, 5736 (2004).

Sulfotransferases: structure, mechanism, biological activity, inhibition and synthetic utility. E. Chapman, M.D. Best, S.R. Hanson, and C.-H. Wong, Angew. Chem. Int. Ed. 43, 3526 (2004).

Rate of enolate formation is not very sensitive to the hydrogen bonding ability of donors to carboxyl oxygen lone pair acceptors; a ramification of the principle of non-perfect synchronization for general-base-catalyzed enolate formation. Z. Zhong, T.S. Snowden, M.D. Best, and E.V. Anslyn, J. Am. Chem. Soc. 126, 3488 (2004).

A fluorescent sensor for 2,3-bisphosphoglycerate using a Europium tetra-N-oxide bis-bipyridine complex for both binding and signaling purposes. M.D. Best, and E.V. Anslyn, Chem. Eur. J. 9, 51 (2003).

Abiotic guanidinium containing receptors for anionic species. M.D. Best, S.L. Tobey, and E.V. Anslyn, Coord. Chem. Rev. 240, 3 (2003).

Preorganized bis-Zinc phosphodiester cleavage catalysts possessing natural ligands: a lesson pertinent to bimetallic artificial enzymes. K. Worm, K. Matsumoto, M.D. Best, and E.V. Anslyn, Chem. Eur. J. 9, 741 (2003).

Metal triggered fluorescence sensing of citrate using a synthetic receptor. L.A. Cabell, M.D. Best, J.L. Lavigne, S.E. Schneider, D.M. Perreault, M.-K. Monahan, and E.V. Anslyn, J. Chem. Soc., Perkin Trans. 2 3, 315 (2001).

Biographical sketch

Dr. Best received his B.S. in chemistry from Boston College in 1997, where he worked with Prof. Lawrence T. Scott on the synthesis of fullerene derivatives. He received his Ph.D. in 2002 from the University of Texas at Austin, where he worked on the design and synthesis of fluorescent sensors for biomolecules in the lab of Prof. Eric V. Anslyn. Following this, he performed post-doctoral research with Prof. Chi-Huey Wong at The Scripps Research Institute. This focused on the application of carbohydrate microarrays for studying cell-surface interactions, as well as the development of heterocycle and nucleotide-derived inhibitors of sulfotransferase enzymes. In 2005, Dr. Best joined the faculty at Tennessee as an assistant professor of organic chemistry.