chemistry department homepage >> faculty >>Susan L. Bane

Susan L. Bane

- Professor, Organic and Biological Chemistry

CONTACT INFORMATION:

Department of Chemistry
State University of New York at Binghamton
Binghamton, NY 13902

e-mail : sbane@binghamton.edu
Phone : (607) 777 2927
Fax : (607) 777 4478

PROFESSIONAL BACKGROUND

  • B.S., Chemistry, Davidson College, 1980
  • Ph.D., Biochemistry, Vanderbilt University, 1983
  • Postdoctoral Research, University of Virginia, 1984-85

RESEARCH INTERESTS

My research interests are in Chemical Biology. Chemical Biology is a relatively new term used to describe the study of the chemistry that underlies all biological structure and processes. We use the principles, theories and tools that have been traditionally applied to small molecules and apply them to investigate biologically important systems. Consequently, we draw from diverse areas of chemistry and biology - ranging from computational chemistry to cell biology - to solve a biological problem.

The biological system that has been the core of our program is the microtubule. Microtubules occupy a central role in the life of a cell. Examine any cellular function that involves movement - division, directional migration, transport - and microtubules are likely to be found. These structures are a dynamic assemblage of several proteins. The central core of the microtubule is composed entirely of the protein tubulin, which is also the most abundant protein in the tubule. The exterior of the microtubule is decorated with proteins collectively termed microtubule-associated proteins, which are implicated in interactions between microtubules and other elements of the cell. Pure tubulin possesses the necessary structural features to assemble and disassemble in the absence of these proteins, and so much of what we know about microtubules has been learned from studying purified tubulin. Understanding the structure and dynamics of microtubules will enhance our understanding of fundamental cellular processes. Of equal importance is the therapeutic application of microtubule chemistry. Microtubules are the target for a number of clinically important drugs effective against a variety of disease states. Microtubule active drugs are especially important in cancer chemotherapy. For example, the Vinca alkaloids have been successfully used for many years to treat leukemia and related neoplasms. Taxol (aka paclitaxel), which is also an antimicrotubule drug, has been described as one of the most important new anticancer drugs of the past 20 years. Taxol quickly found its place in the chemical arsenal against cancer and is highly effective against some notoriously difficult tumors. Understanding the molecular interactions of these drugs with the microtubule receptor will spur the development of newer, more effective anticancer drugs.

Below are a few examples of research programs currently in progress in my lab.

Molecular mechanism of Taxol chemotherapy. Taxol has a complicated structure - difficult to synthesize and conformationally mobile. The next generation of Taxol-like drugs will ideally retain the structural features required for potency but possess much simpler structures. Design of such compounds will rely on a detailed understanding of the molecular interactions between Taxol and microtubules.

Site-specific fluorescent labeling of proteins. Fluorescence spectroscopy is the most common, powerful and sensitive optical technique used in chemical biology. Selective observation of a biological phenomenon is possible when components of the system possess an optical signal that is distinct from their surroundings, which normally requires the use of an exogenous fluorophore.

In our lab, we are trying to develop a method for fluorescently labeling proteins that is versatile yet highly specific, compatible with living systems, and capable of monitoring phenomena temporally and spatially.

This labeling project includes:

  • Synthesis of suitable fluorescent probes and their photochemical properties.
  • Background spectroscopic characterizations of these fluorophores for site specific protein labeling in vitro and living cells.
  • Incorporation of the reactive amino acids into protein and labelling of them with fluorophores.

Molecular mechanisms of colchicine and related drugs. Colchicine is one of the oldest drugs in the pharmacopoeia. Medical use of colchicine has been almost continuous for 1400 years, and the drug is still a treatment of choice for acute gout. Colchicine acts by binding to a single site on unassembled tubulin, subsequently inhibiting tubulin polymerization. A surprising number of drugs bind to the same site as colchicine, including podophyllotoxin, nocodazole, and combretastatin, and new molecules with colchicine-site activity continue to be discovered. We are attempting to formulate a unified mechanism for the association of such chemically diverse structures with a single receptor site on the protein.

The techniques used to study this and other ligand-receptor systems are derived from a variety of disciplines, including, organic, physical, and biological chemistry. Specific examples are organic synthesis, protein purification and characterization, and spectroscopic techniques such as absorption, emission, and NMR spectroscopy.


SELECTED PUBLICATIONS

  1. “Design, synthesis and biological evaluation of bridged epothilone D analogues.” Chen QH, Ganesh T, Brodie P, Slebodnick C, Jiang Y, Banerjee A, Bane S, Snyder JP, Kingston DG. (2008) Organic and Biomolecular Chemistry 6, 4542-4552. [PubMed]

  2. “Synthesis of boron dipyrromethene fluorescent probes for bioorthogonal labeling.” Dilek O and Bane S. (2008) Tetrahedron Letters 49, 1413-1416.

  3. “Enhanced microtubule binding and tubulin assembly properties of conformationally constrained paclitaxel derivatives.” Shanker N, Kingston DG, Ganesh T, Yang C, Alcaraz AA, Geballe MT, Banerjee A, McGee D, Snyder JP, Bane S. (2007) Biochemistry 46, 11514-11527. [PubMed]

  4. “Evaluation of the tubulin-bound paclitaxel conformation: synthesis, biology, and SAR studies of C-4 to C-3' bridged paclitaxel analogues.”Ganesh T, Yang C, Norris A, Glass T, Bane S, Ravindra R, Banerjee A, Metaferia B, Thomas SL, Giannakakou P, Alcaraz AA, Lakdawala AS, Snyder JP, Kingston DG. (2007) Journal of Medicinal Chemistry 50, 713-725. [PubMed]

  5. “Rotational-echo double-resonance NMR distance measurements for the tubulin-bound Paclitaxel conformation.” Paik Y, Yang C, Metaferia B, Tang S, Bane S, Ravindra R, Shanker N, Alcaraz AA, Johnson SA, Schaefer J, O'Connor RD, Cegelski L, Snyder JP, Kingston DG. (2007) Journal of the American Chemical Society 129, 361-70. [PubMed]

  6. “Promotion of tubulin assembly by poorly soluble taxol analogs.” Sharma S, Ganesh T, Kingston DG, Bane S. (2007) Analytical Biochemistry 360, 56-62.[PubMed]

  7. “Bridging converts a noncytotoxic nor-paclitaxel derivative to a cytotoxic analogue by constraining it to the T-Taxol conformation.” Tang S, Yang C, Brodie P, Bane S, Ravindra R, Sharma S, Jiang Y, Snyder JP, Kingston DG. (2006) Organic Letters 8, 3983-3986. [PubMed]

  8. “Design, synthesis, and bioactivity of simplified paclitaxel analogs based on the T-Taxol bioactive conformation.” Ganesh T, Norris A, Sharma S, Bane S, Alcaraz AA, Snyder JP, Kingston DG. (2006) Bioorganic and Medicinal Chemistry 14, 3447-3454. [PubMed]

  9. “The taxol pharmacophore and the T-taxol bridging principle.” Kingston DG, Bane S, Snyder JP. (2005) Cell Cycle 4, 279-289. Review. [PubMed]

  10. “The bioactive Taxol conformation on beta-tubulin: experimental evidence from highly active constrained analogs.” Ganesh T, Guza RC, Bane S, Ravindra R, Shanker N, Lakdawala AS, Snyder JP, Kingston DG. (2004) Proceedings of the National Academy of Sciences 101, 10006-10011. [PubMed]

  11. “Design, synthesis, and bioactivities of steroid-linked taxol analogues as potential targeted drugs for prostate and breast cancer.” Liu C, Strobl JS, Bane S, Schilling JK, McCracken M, Chatterjee SK, Rahim-Bata R, Kingston DG. (2004) Journal of Natural Products 67, 152-159. [PubMed]

  12. “A fluorescence-based high-throughput assay for antimicrotubule drugs.” Barron DM, Chatterjee SK, Ravindra R, Roof R, Baloglu E, Kingston DG, Bane S. (2003) Analytical Biochemistry 315, 49-56. [PubMed]

  13. “Synthesis and biological evaluation of C-3'NH/C-10 and C-2/C-10 modified paclitaxel analogues.” Baloglu E, Hoch JM, Chatterjee SK, Ravindra R, Bane S, Kingston DG. Bioorganic and Medicinal Chemistry 11, 1557-1568. [PubMed]

  14. “Design and synthesis of a combinatorial chemistry library of 7-acyl, 10-acyl, and 7,10-diacyl analogues of paclitaxel (taxol) using solid phase synthesis.” Jagtap PG, Baloglu E, Barron DM, Bane S, Kingston DG. (2002) Journal of Natural Products 65, 1136-42. [PubMed]

  15. “Interaction of tubulin with a new fluorescent analogue of vinblastine.” Chatterjee SK, Laffray J, Patel P, Ravindra R, Qin Y, Kuehne ME, Bane SL. (2002)Biochemistry41, 14010-14018. [PubMed]

  16. “Synthesis and Antimicrotubule Activity of Combretatropone Derivatives.”Janik ME and Bane SL. (2002) Bioorganic and Medicinal Chemistry 10, 1895-1903. [PubMed]

  17. “The Syntheses of 16a’-homo-Leurosidine and 16a’-homo-Vinblastine. Generation of Atropisomers.”Kuehne ME, Qin Y, Hout AE and Bane SL. (2001) Journal of Organic Chemistry 66, 5317-5328. [PubMed]

  18. “Synthesis and Microtubule Binding of Fluorescent Paclitaxel Derivatives.”Baloglu E, Kingston DGI, Patel P, Chatterjee SK and Bane SL. (2001) Bioorganic and Medicinal Chemistry Letters 11, 2249-2252. PubMed]

  19. “Synthesis and Biological Evaluation of Novel Macrocyclic Paclitaxel Analogs.”Metaferia BB, Hoch J, Glass TE, Bane SL, Chatterjee SK, Snyder JP, Lakdawala A, Cornett B and Kingston DGI. (2001) Organic Letters 3, 2461-2464. [PubMed]

  20. “Baccatin III Induces Tubulin to Assemble into Long Microtubules”Chatterjee SK, Barron DM, Vos S and Bane S. (2001) Biochemistry 40, 6964-6970. [PubMed]

  21. “Equilibrium Studies of a Fluorescent Paclitaxel Derivative Binding to Microtubules”Li Y, Edsall RJ, Jagtap PG, Kingston DGI and Bane S. (2000) Biochemistry 39, 616-623. [PubMed]

  22. “Conformation of Microtubule-Bound Paclitaxel Determined by Fluorescence Spectroscopy and REDOR NMR”Li Y, Poliks B, Cegelski L, Poliks M, Grycznski Z, Piszczek G, Jagtap PG, Studelska DJ, Kingston DGI, Schaefer J and Bane S. (2000) Biochemistry 39, 281-291. [PubMed]

  23. “Distances Between the Paclitaxel, Colchicine and Exchangeable GTP Binding Sites on Tubulin.”Han Y, Malak H, Chaudhary AG, Chordia MD, Kingston DGI, and Bane S. (1998) Biochemistry 37, 6636-6644. [PubMed]

  24. “Capillary Isoelectric Focusing with Anionic Coated Capillaries.” Whynot DM, Hartwick RA and Bane S. (1997) Journal of Chromatography A 767, 231-239.

  25. “Interaction of a Fluorescent Derivative of Paclitaxel (Taxol) with Microtubules and Tubulin-Colchicine.”Han Y, Chaudhary AG, Chordia MD, Sackett DL, Perez-Ramirez B, Kingston DGI and Bane S. (1996) Biochemistry 35, 14173-14183. [PubMed]

  26. “Conformational Analysis of Colchicinoids Containing an Electron Deficient Aromatic Ring on the B Ring.”Pyles EA and Hastie (Bane) SB. (1993) Journal of Organic Chemistry 58, 2751-2759.

  27. “Effect of the B Ring and the C-7 Substituent on the Kinetics of Colchicinoid-Tubulin Associations.”Pyles EA and Hastie SB. (1993) Biochemistry 32, 2329-2336. [PubMed]

  28. “Synthesis and Tubulin Binding of Novel C-10 Analogues of Colchicine”Staretz ME and Hastie SB. (1993) Journal of Medicinal Chemistry 36, 758-764. [PubMed]

  29. “Interactions of Colchicine with Tubulin.”Hastie SB. (1991) Pharmacology and Therapeutics 51, 377-401. Review. [PubMed]

  30. “Effect of Tubulin Binding and Self-Association on the Near-Ultraviolet Circular Dichroic Spectra of Colchicine and Analogs.”Chabin RM, Feliciano F and Hastie SB. (1990) Biochemistry 29, 1869-1875. [PubMed]

 
 
© Department of Chemistry, State University of New York at Binghamton, Binghamton, NY 13902-6000