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
NSF CAREER Awardee
Qualls, M.; Hagewood, H.; Lou, J.; Mattern-Schain, S.I.; Zhang. X.; Mountain, D.J.; Best, M.D.* Bis-boronic acid liposomes for carbohydrate recognition and cellular delivery. ChemBioChem. In Press.
Qualls, M.L.; Lou, J.; McBee, D.P.; Baccile, J.A.; Best, M.D.* Cyclic disulfide lipids for membrane functionalization and cellular delivery. Chem. Eur. J. 2022 28(45), e2022011. DOI: 10.1002/chem.202201164.
Lou, J.; Qualls, M.L.; Hudson, M.M.; Baccile, J.A.; Best, M.D.* Reactive oxygen species (ROS) activated liposomal cell delivery using a boronate-caged guanidine lipid. Chem. Eur. J. 2022, 28(46), e202201057. DOI: 10.1002/chem.202201057.
Bottcher, S.; Lou, J.; Best, M.D.* Liposome triggered content release through molecular recognition of inositol trisphosphate. Chem. Commun. 2002, 58, 4520-4523, DOI: 10.1039/d2cc00951j.
Lou, J.; Schuster, J.; Barrera, F.N.; Best, M.D.* ATP-Responsive liposomes developed by screening lipid switches designed to undergo conformational changes upon binding phosphorylated metabolites. J. Am. Chem. Soc. 2022, 144, 3746-3756. DOI 10.1021/jacs.2c00191.
Gray, A.L.; Sawaya, M.R.; Acharyya, D.; Lou, J.; Edington, E.; Best, M.D.; Prosser, R.A.; Eisenberg, D.S.; Do, T.D.* Atomic view of an amyloid dodecamer exhibiting selective cellular toxic vulnerability in acute brain slices. Protein Sci. 2022, 31(3), 716-727. DOI 10.1002/pro.4268
Sagar, R.; Lou, J.; Watson, A.; Best, M.D.* Zinc Triggered Release of Encapsulated Cargo from Liposomes via a Synthetic Lipid Switch. Bioconjugate Chem. 2021, 32(12), 2485-2496. DOI: 10.1021/acs.bioconjchem.1c00425.
Qualls, M.; Sagar, R.; Lou, J.; Best, M.D. Demolish and rebuild: Controlling membrane self-assembly using toward triggered release and artificial cells. J. Phys. Chem. B. 2021, 125, 12918-12933. DOI: 10.1021/acs.jpcb.1c07406.
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.
Ricks, T.J.; Cassilly, C.D.; Carr, A.J.; Alam, S.; Tscherch, K.; Yokley, T.W.; Workman, 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. DOI 10.1002/cbic.201800248.
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. DOI 10.1002/chem.201803389.
Mattern-Schain, S.I.; Fisher, R.K.; West, P.C.; Kirkpatrick, S.S.; Best, M.D.;* Mountain, D.J.H.* Cell mimetic liposomal nanocarriers for tailored delivery of vascular therapeutics. Chem. Phys. Lipids. 2019, 218, 149-157. DOI: 10.1016/j.chemphyslip.2018.12.009.
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.; Mattern-Schain, S.I.; Best, M.D.* Targeting and triggered release using lipid-based supramolecular assemblies as medicinal nanocarriers. In: Comprehensive Supramolecular Chemistry II, Atwood, J.L. (ed.), 2017, vol. 5, 329-364. (Book Chapter)
Fisher, R.K.; Mattern-Schain, S.I.; Best, M.D.; Kirkpatrick, S.S.; Freeman, M.B.; Grandas, O.H.;Mountain, D.J.H.* Improving the efficacy of liposome-mediated vascular gene therapy via lipid surface modifications. Journal of Surgical Research 2017, 219, 136-144.
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 liposomal release through a phosphatidylcholine analogue 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.