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Gary A. Sulikowski

Title and Contact Information

Stevenson Professor of Chemistry
Office: 12415-F MRB IV
Phone: (615) 343-4155
EmailWebsite

Education

Ph.D., University of Pennsylvania, 1989

Specialties

VICB
Organic Chemistry
Natural Products
Medicinal Chemistry
Chemical Biology
Biosynthesis
Bioorganic Chemistry
Biochemistry

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Sulikowski

Research

Total Synthesis of Complex Natural Products A longstanding interest of the Sulikowski research group is the total synthesis of structurally complex natural products. The selection of natural products as synthetic targets is based on structural novelty, scarcity in nature and/or biological activity. Among these three selection criteria structure novelty is of paramount importance, as this often leads to the development of novel synthetic design and strategy. Natural products of current interest to the Sulikowski group are shown below and include heterocyclic (bielschowskysin and upenamide), polyketide (ammocidin D), aromatic polyketide (hibarimicinone and lomaiviticinone) and lipid derived (bicyclobutane fatty acid) synthetic targets. To date, we have completed the synthesis of urdamycinone B, (+)-SF 2315A, (+)-5-epiindolizidine 167B, landomycin A hexasaccharide, apoptolidinone and (+)-haliclonacyclamine C.

 

 

Chemical Biology of Natural Products and Small Molecules In addition to the total synthesis of natural products we are also investigating various aspects of chemical biology associated with this fascinating group of small molecules (natural products) discovered in living systems. Our interests can be generally divided into two areas. First, we aim to define biosynthetic pathways leading to complex natural products. And consider if this method of assembly can be taken to our advantage in the laboratory preparation of natural products and derivatives. For example, we have studied the biosynthesis of phomoidride B (which involves the remarkable dimerization-oxidation pathway starting from a simple unsaturated anhydride). In collaboration with the Bachmann group we are also studying the biosynthesis of the cell-selective cytotoxic macrolide apoptoldin A. A second area of interest is the discovery and study of the effects of natural products on biological systems, including cell cytotoxicity and interaction with cellular targets. A majority of these studies are conducted in collaboration with members of the Vanderbilt Institute of Chemical Biology.

Sulikowski figure5

Selected Publications

Williams CH,  Hempel JE,  Hao J,  Frist AY,  Williams MM,  Fleming JT ,  Sulikowski GA,  Cooper MK,  Chiang C,  Hong CC An in vivo chemical genetic screen identifies phosphodiesterase 4 as a pharmacological target for hedgehog signaling inhibition. Cell Reports.   2015, 11(1):43-50. 

DeGuire SM, Earl DC, Du Y, Crews BA, Jacobs AT, Ustione A, Daniel C, Chong KM, Marnett LJ, Piston DW, Bachmann BO, Sulikowski GA. Fluorescent probes of the apoptolidins and their utility in cellular localization studies. Angewandte Chemistry International Ed in English. 2015, 54(3):961-4.

Evans SM, Kim K, Moore CE, Uddin MI, Capozzi ME, Craft JR, Sulikowski GA, Jayagopal A. Molecular probes for imaging of hypoxia in the retina. Bioconjugate Chemistry. 2014, 25(11):2030-7.

Romaine IM, Taylor RW, Saidu SP, Kim K, Sulikowski GA, Zwiebel LJ, Waterson AG.Narrow SAR in odorant sensing Orco receptor agonists. Bioorganic & Medicinal Chemistry Letters. 2014, 24(12):2613-6.

Mike LA, Choby JE, Brinkman PR, Olive LQ, Dutter BF, Ivan SJ, Gibbs CM, Sulikowski GA, Stauff DL, Skaar EP. Two-component system cross-regulation integrates Bacillus anthracis response to heme and cell envelope stress. PLoS Pathogens. 2014, 10(3):e1004044.

Wen, W.D.; Wu, W.J.; Romaine, I.M.; Kaufmann, K.; Du, Y.; Sulikowski, G.A.; Weaver, C.D.; Lindsley, C.W. Discovery of 'molecular switches' within a GIRK activator scaffold that afford selective GIRK inhibitors. Bioorganic & Medicinal Chemistry Letters. 2013, 23 (16): 4562-4566.

Mike, L.A.; Dutter, B.F.; Stauff, D.L.; Moore, J.L.; Vitko, N.P.; Aranmolate, O.; Kehl-Fie, T.E.; Sullivan, S.; Reid, P.R.; DuBois, J.L.; Richardson, A.R.; Caprioli, R.M.; Sulikowski, G.A.; Skaar, E.P. Activation of heme biosynthesis by a small molecule that is toxic to fermenting Staphylococcus aureus. Proceedings of The National Academy of Sciences of The United States of America. 2013, 110 (20): 8206-8211.

Kaufmann, K.; Romaine, I.; Days, E.; Pascual, C.; Malik, A.; Yang, L.Y.; Zou, B.D.; Du, Y.; Sliwoski, G.; Morrison, R.D.; Denton, J.; Niswender, C.M.; Daniels, J.S.; Sulikowski, G.A.; Xie, X.M.; Lindsley, C.W.; Weaver, C.D. ML297 (VU0456810), the First Potent and Selective Activator of the GIRK Potassium Channel, Displays Antiepileptic Properties in Mice. ACS Chemical Neuroscience. 2013, 4 (9): 1278-1286.

Thompson, M.K.; Keithly, M.E.; Harp, J.; Cook, P.D.; Jagessar, K.L.; Sulikowski, G.A.; Armstrong, R.N. Structural and Chemical Aspects of Resistance to the Antibiotic Fosfomycin Conferred by FosB from Bacillus cereus. Biochemistry. 2013, 52 (41): 7350-7362.

Ramos-Hunter, S.J.; Engers, D.W.; Kaufmann, K.; Du, Y.; Lindsley, C.W.; Weaver, C.D.; Sulikowski, G.A. Discovery and SAR of a novel series of GIRK1/2 and GIRK1/4 activators. Bioorganic & Medicinal Chemistry Letters. 2013, 23 (18): 5195-5198.

Mike, L.A.; Dutter, B.F.; Stauff, D.L.; Moore, J.L.; Vitko, N.P.; Aranmolate, O.; Kehl-Fie, T.E.; Sullivan, S.; Reid, P.R.; DuBois, J.L.; Richardson, A.R.;Caprioli, R.M.; Sulikowski, G.A.; Skaar, E.P. Activation of heme biosynthesis by a small molecule that is toxic to fermenting Staphylococcus aureus. Proceedings of The National Academy of Sciences of The United States of America. 2013, 110 (20): 8206-8211.

Taylor, R.W.; Romaine, I.M.; Liu, C.; Murthi, P.; Jones, P.L.; Waterson, A.G.; Sulikowski, G.A.; Zwiebel, L.J. Structure-Activity Relationship of a Broad-Spectrum Insect Odorant Receptor Agonist. ACS Chemical Biology. 2012, 7 (10): 1647-1652.

Baranczak, A.; Sulikowski, G.A. Cascade assembly of the benz[a]anthraquinone ring system common to the angucycline antibiotics. Tetrahedron Letters. 2012, 53 (11): 1345-1346.

Baranczak, A.; Sulikowski, G.A. Synthetic Studies Directed toward Dideoxy Lomaiviticinone Lead to Unexpected 1,2-Oxazepine and Isoxazole Formation. Organic Letters. 2012, 14 (4): 1027-1029.

Melancon, B.J.; Lamers, A.P.; Bridges, T.M.; Sulikowski, G.A.; Utley, T.J.; Sheffler, D.J.; Noetzel, M.J.; Morrison, R.D.; Daniels, J.S.; Niswender, C.M.; Jones, C.K.; Conn, P.J.; Lindsley, C.W.; Wood, M.R. Development of a more highly selective M-1 antagonist from the continued optimization of the MLPCN Probe ML012. Bioorganic & Medicinal Chemistry Letters. 2012, 22 (2): 1044-1048.

DeGuire, S.M.; Ma, S.T; Sulikowski, G.A. Synthesis of a Bicyclobutane Fatty Acid Identified from the Cyanobacterium Anabaena PCC 7120. Angewandte Chemie-Internationa Edition. 2011, 50 (42): 9940-9942.

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