Michael D. Best
Associate Professor & Director of Graduate Studies
Organic Chemistry
Bio-organic, supramolecular and medicinal chemistry
B.S., Boston College (1997)
Ph.D., The University of Texas at Austin (2002)
NSF CAREER Awardee
Additional Information
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
Bostic, H.E.; Smith, M.D.; Poloukhtine, A.A.; Popik, V.V.; Best, M.D. Membrane labeling and immobilization via copper-free click chemistry. Chem. Commun. 2012, 48, 1431-1433.
Rowland, M.M.; Bostic, H.E.; Gong, D.; Lucas, N.; Cho, W.; Best, M.D. Microarray analysis of Akt PH domain binding employing synthetic biotinylated analogs of all seven phosphoinositide headgroup isomers. Chem. Phys. Lipids 2012, 165, 207-215.
Rowland, M.M.; Bostic, H.E.; Gong, D.; Speers, A.E.; Lucas, N.; Cho, W.; Cravatt, B.F. Best, M.D. Phosphatidylinositol (3,4,5)-trisphosphate activity probes for the labeling and proteomic characterization of protein binding partners. Biochemistry. 2011, 50, 11143−11161.
Do-Thanh, C.-L.; Khanal, N.; Lu, Z.; Cramer, S.A.; Jenkins, D.M.*; Best, M.D.* Chloride binding by a polyimidazolium macrocycle detected via fluorescence, NMR and X-ray crystallography. Tetrahedron 2012, 68, 1669-1673.
He, J.; Gajewiak, J.; Scott, J.L.; Gong, D.; Ali, M.; Best, M.D.; Prestwich, G.D.; Stahelin R.V.; Kutateladze, T.G. Metabolically stabilized derivatives of phosphatidylinositol 4-phosphate: Synthesis and applications. Chem. Biol. 2011, 18, 1312-1319.
Kooijman, E.E.; Kuzenko, S.R.; Gong, D.; Best, M.D.; Folkesson, H.G. Phophatidylinositol-4,5-bisphosphate stimulates alveolar epithelial fluid clearance in male and female adult rats. Am. J. Physiol.-Lung Cell. Mol. Physiol. 2011, 301, L804–L811.
Best, M.D.* Recent developments in the generation and application of lipid probes. ASBMB Today 2011, August edition, 28-29.
Best, M.D.*; Rowland, M.M.; Bostic, H.E. Exploiting bioorthogonal chemistry to elucidate protein-lipid binding interactions and other biological roles of phospholipids. Acc. Chem. Res. 2011, 44(9), 686–698.
Smith, M.D.; Best, M.D.* Characterization of protein–membrane binding interactions via a microplate assay employing liposome immobilization. Bioconjugation Protocols, 2nd edition, Editor: Sonny S. Mark. 2011, 477-489.
Do-Thanh, C.-L.; Rowland, M.M.; Best, M.D.* Fluorescent bis-cyclen tweezer receptors for inositol (1,4,5)-trisphosphate. Tetrahedron 2011, 67, 3803-3808.
Bolen, A.L.; Naren , A.P.; Yarlagadda, S.; Beranova-Giorgianni, S.; Chen, L. Norman, D.; Baker, D.L.; Rowland, M.M.; Best, M.D.; Sano T., Tsukahara, T.; Liliom, K.; Igarashi, Y.; Tigyi, G.* The phospholipase A 1 activity of lysophospholipase A-I links platelet activation to LPA production during blood coagulation. J. Lipid Res. 2011, 52, 958-970.
Rowland, M.M.; Best, M.D.* Reeling in the Catch: Advancing Cleavable Linkers for Proteomics. Chem. Biol. 2010, 17, 1166-168. (Invited preview article).
Photocurrent generation from porphyrin/fullerene complexes assembled in a tethered lipid bilayer. Zhan, W.; Jiang, K.; Smith, M.D.; Bostic, H.E.; Best, M.D.; Auad, M.L.; Ruppel, J.V.; Kim, C.; Zhang, X.P. Langmuir. 2010, 26(19), 15671-15679.
Inositol polyphosphates, diphosphoinositol polyphosphates and phosphatidylinositol polyphosphate lipids: Structure, synthesis, and development of probes for studying biological activity. Best, M.D.; Zhang, H.; and Prestwich, G.D. Nat. Prod. Rep. 2010, 27, 1403-1430.
Optimization of a pipemidic acid-based autotaxin inhibitor. Hoeglund, A.B.; Bostic, H.E.; Howard, A.L.; Wanjala, I.W.; Best, M.D.; Baker, D.L.; Parrill, A.L. J. Med. Chem. 2010, 53, 1056–1066.
Modular synthesis of biologically active phosphatidic acid probes using click chemistry. M.D. Smith,
C.G. Sudhahar, D. Gong, R.V. Stahelin, M.D. Best, Mol. Biosyst.
2009, 5, 962-972.
Click chemistry and bioorthogonal reactions: Unprecedented selectivity in the labeling of biological molecules. M.D. Best, Biochemistry, 2009, 48, 6571-6584.
Synthesis of modular headgroup conjugates corresponding to all seven phosphatidylinositol polyphosphate isomers for convenient probe generation. D. Gong, H.E. Bostic, M.D. Smith, M.D. Best, Eur. J. Org. Chem. 2009, 24, 4170-4179.
Modular synthesis of bis(monoacylglycero)phosphate for convenient access to analogues bearing hydrocarbon and perdeuteratedacyl chains of varying length. M.M. Rowland, M.D.; Best, Tetrahedron 2009, 65, 6844-6849.
Microplate-based characterization of protein-phosphoinositide binding interactions using a synthetic biotinylated headgroup analogue. D. Gong, M.D. Smith, D. Manna, H.E. Bostic, W. Cho, M.D. Best, Bioconjugate Chem. 2009, 20, 310-316.
Microplate-based analysis of protein-membrane binding interactions via immobilization of whole liposomes containing a biotinylated anchor. E.A. Losey, M.D. Smith, M. Meng, M.D. Best, Bioconjugate Chem. 2009, 20, 376-383.
Synthesis and Convenient functionalization of azide-labeled diacylglycerol analogues for modular access to biologically active lipid probes. M.D. Smith, D. Gong, D. Sudhahar, J.C. Reno, R.V. Stahelin, M.D. Best, Bioconjugate Chem. 2008, 19, 1855-1863.
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. 2006, 103, 15-20.
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.
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. 2005, 13, 4622-4626.
Covalent display of oligosaccharide arrays inmicrotiter 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. 2004, 126, 8640-8641.
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 2004, 5, 811-819.
Chemoenzymatic synthesis of oligosaccharides and glycoproteins. S.R. Hanson, M.D. Best, M.C. Bryan, and C.-H. Wong, Trends Biochem. Sci. 2004, 29, 656-663.
Sulfatases: structure, mechanism, biological activity, inhibition and synthetic utility. S.R. Hanson, M.D. Best, and C.-H. Wong, Angew. Chem., Int. Ed. 2004, 43, 5736-5763.
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. 2004, 43, 3526-3548.
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. 2004, 126, 3488-3495.
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. 2003, 9, 51-57.
Abiotic guanidinium containing receptors fo ranionic species. M.D. Best, S.L. Tobey, and E.V. Anslyn, Coord. Chem. Rev. 2003, 240, 3-15.
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. 2003, 9, 741-747.
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.
Michael D. Best
353 Buehler Hall
Knoxville, TN 37996-1600
Phone: (865) 974-8658
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