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Michael D. Best



Research in the Best group entails bio-organic, synthetic organic, medicinal and supramolecular chemistry. This generally involves the design, synthesis and study of organic molecules for applications pertaining to biological systems. Our lab has a particular emphasis on lipid membranes, which are at the forefront of biomedical research since lipids control critical biological pathways relevant to disease, and are beneficial for applications such as drug delivery. One area of research in the group involves the development of smart liposomes for drug delivery through the design of responsive lipid structures. Additionally, we develop functionalized lipid probes that can be applied to elucidate the roles of lipids in biological processes. These projects utilize synthetic organic chemistry to access designer lipid targets, followed by biological and analytical chemistry studies to study and apply these compounds.


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.


B.S., Boston College (1997)
Ph.D., The University of Texas at Austin (2002)

Awards and Recognitions

Ziegler Professorship


Fisher, R.K.; West, P.C.; Mattern-Schain, S.I.; Best, M.D.; Kirkpatrick, S.S.; Dieter, R.A.; Arnold, J.D.; Buckely, M.R.; McNally, M.M.; Freeman, M.B.; Grandas, O.H.; Mountain D.J.H. Advances in the formulation and assembly of non-cationic lipid nanoparticles for the medical application of gene therapeutics. Nanomaterials 2021, 11(3), 825. DOI: 10.3390/nano11030825

Olson, J.; Hu, Z.; Best, M.D.; Jensen, L.; Camden, J.P. Surface-enhanced hyper-Raman scattering of rhodamine 6G isotopologues: Assignment of low vibrational frequencies. J. Chem. Phys. 2021, 154, 034703. DOI: 10.1063/5.0031679

Ancajas, C.; Best, M.D.* Metabolic labeling of glycerophospholipids via clickable analogs derivatized at the lipid headgroup. Chem. Phys. Lipids 2020, 232, 104971. DOI 10.1016/j.chemphyslip.2020.104971.

Lou, J.; Best, M.D.* Strategies for altering lipid self-assembly to trigger liposome cargo release. Chem. Phys. Lipids 2020, 232, 104966. DOI 10.1016/j.chemphyslip.2020.104966.

Lou, J. Best, M.D.* Reactive oxygen species-responsive liposomes via boronate-caged phosphatidylethanolamine. Bioconjugate Chem. 2020, 31, 2220-2230. DOI 10.1021/acs.bioconjchem.0c00397.

Lou, J.; Best, M.D. Calcium-responsive liposomes: Toward ion-mediated targeted drug delivery. Meth. Enzymol. 2020, 640, 105-129. DOI 10.1016/bs.mie.2020.04.005.

Lou, J.; Best, M.D. A general approach to enzyme-responsive liposomes. Chem. Eur. J. 2020, 26, 8597 –8607. DOI 10.1002/chem.202000529.

Lou, J.; Zhang, X.; Best, M.D. Lipid switches: Stimuli-responsive liposomes via conformational isomerism driven by molecular recognition. Chem. Eur. J. 2019, 25, 20-25.

Ricks, T.J.; Cassilly, C.D.; Carr, A.J.; Alam, S.; Tscherch, K.; Yokley, T.W.; Worman, C.E.; Alves, D.S.; Morrell-Falvey, J.L.; Barrera, F.N.; Reynolds, T.B.; Best, M.D.* Labeling of phosphatidylinositol lipid products in cells via metabolic engineering using a clickable myo-inositol probe. ChemBioChem. 2019, 20, 172-180.

Zhang, X.; Alves, D.S.; Lou, J.; Hill, S.D.; Barrera, F.N.; Best, M.D.* Boronic acid liposomes for cellular delivery and content release driven by carbohydrate binding. Chem. Commun. 2018, 54, 6169-6172.

Lou, J.; Carr, A.J.; Watson, A.J.; Mattern-Schain, S.I.; Best, M.D.* Calcium-responsive liposomes via a synthetic lipid switch. Chem. Eur. J. 2018, 24, 3599-3607.

Zhang, X.; Zhang, S.; Baek, S.J.; Best, M.D.* A boronic acid assay for the detection of mucin-1 glycoprotein from cancer cells. ChemBioChem  2017, 18, 1578-1582.

Whitehead, S.A.; McNitt, C.D.; Mattern-Schain, S.I.; Carr, A.J.; Alam, S.; Popik, V.V.; Best, M.D. Artificial membrane fusion triggered by strain-promoted alkyne-azide cycloaddition. Bioconjugate Chem. 2017, 28, 923-932.

Alam, S.; Alves, D.S.; Whitehead, S.A.; Bayer, A.M.; McNitt, C.D.; Popik, V.V.; Barrera F.N.; Best, M.D. A clickable and photocleavable lipid analogue for cell membrane delivery and release. Bioconjugate Chem. 2015, 26, 1021-1031.

Best, M.D.* Global approaches for the elucidation of phosphoinositide-binding proteins. Chem. Phys. Lipids 2014, 182, 19-28.

Bayer, A.M.; Alam, S.; Mattern-Schain, S.I.; Best, M.D. Triggered release of molecular cargo from liposomes via a phosphatidylcholine analog bearing a photocleavable moiety embedded within the sn-2 acyl chain. Chem. Eur. J. 2014, 20(12), 3350-3357.

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.

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.

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.

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.

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. 

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