dept of biochem

homefacultyresearch areasgraduate programpostdocscoursesseminarsresourcescontact uslinksdirectory

William W. Bachovchin

M&V 613A
136 Harrison Ave.
Boston, MA 02111
william.bachovchin@tufts.edu

office: 617-636-6881
lab: 617-636-6882

William W. Bachovchin, Ph.D.

Professor, Tufts Department of Biochemistry

Director of Tufts Biological NMR Center

Wake Forest University, Winston-Salem, NC
B.S. 1970 Biology

California Institute of Technology, Pasadena, CA
Ph.D. 1977 Chemistry

California Institute of Technology, Pasadena, CA
Fellow 1978 15N NMR:SerineProteases

Harvard Medical School, Boston, MA
Fellow 1979 Zn Metallopeptidases

Links:

Issued Patents

Lab Members

Recent Publications

Research Summary:

My research group uses NMR spectroscopy to solve the three dimensional structures of biological macromolecules, as exemplified by our work on the origin binding domain of SV40 T antigen. We also use NMR to elucidate key interactions within enzyme active sites as exemplified by our work on the serine proteases. We are primarily interested in the biological functions of serine proteases. Our work in this area has a substantial drug design and discovery component. This includes very strong in-house organic synthesis and assay capabilities. Technology that grew out of our drug design and discovery work on serine proteases has led to the establishment of two companies, Point Therapeutics and Arisaph Pharmaceuticals.

 

Lab Members:

Faculty
   


Postdoctoral Associates

Present
FangMing

Past

  • Ulrich L. Guenther, Ph.D.
  • William G. Gutheil, Ph.D.
  • George R. Flentke, Ph.D.
  • Thara Rao, Ph.D.


Graduate Students and Trainees

Present

Past

  • Daniel P. O'Connell, Ph.D. '07
  • Sarah E. Poplawski, Ph.D., '06
  • Elizabeth M. Bradshaw, Ph.D., '05
  • Kristin E. Coffman Haddad, Ph.D., '04
  • Charles P. Plant, M.D., Ph.D., '03
  • Elissa L. Ash, M.D., Ph.D., '00
  • Ekaterina V. Torchilin, Ph.D., '99
  • Xuelian Luo, Ph.D., '98
  • Regina M. Day, Ph.D., '95
  • Elisabeth Tsilikounas, Ph.D., '93
  • Matthew P. Vincent, Ph.D., '92
  • Shauna Farr-Jones, Ph.D.,'89
  • Winona Y. L. Wong, B.S., '85
  • Sharon Switzman, B.S., '82


Lab Managers, Research Assistants, Technicians, and Staff

>
 
 
 
   
 

 

Publications

Selected peer-reviewed

  • Lai, J. H.; Wu, W., et al. (2007) "Synthesis and Characterization of Constrained Peptidomimetic Dipeptidyl Peptidase IV Inhibitors: Amino-Lactam boroAlanines." J. Med. Chem., 50(10): 2391-2398.

  • Reese, D, K.; Meinke, G., et al. (2007) "Analyses of the interaction between the origin binding domain from simian virus 40 T antigen and single-stranded DNA provide insights into DNA unwinding and initiation of DNA replication." J. Virol., 80(24): 12248-12259.

  • Lai, J. H., Liu, Y., et al. (2006) "Synthesis and Structural Investigation of Internally Coordinated alpha-Amidoboronic Acids." J. Org. Chem., 71(2): 512-519.

  • Haddad, K.C., Sudmeier, J.L., et al. (2005). “Alpha-lytic protease can exist in two separately stable conformations with different His57 mobilities and catalytic activities.” Proc. Natl. Acad. Sci. USA, 102(4):1006-1011.

  • Sudmeier JL, Zhou Y, et al. (2005). "Autochelation in dipeptide boronic acids: pH-dependent structures and equilibria of Asp-boroPro and His-boroPro by NMR spectroscopy." J. Am. Chem. Soc. 127(22):8112-8119.

  • Cheng, J.D., Valianou, M., et al. (2005). "Abrogation of fibroblast activation protein enzymatic activity attenuates tumor growth." Mol. Cancer Ther., 4(3): 351-360.

  • Bradshaw, E.M., Sanford, D.G., et al. (2004). “T antigen origin-binding domain of simian virus 40: determinants of specific DNA binding.” Biochemistry, 43(22):6928-6936.

  • Krishnaswamy, S., Duan, S.X., et al. (2003). “Serotonin (5-hydroxytryptamine) glucoronidation in vitro: assay development, human liver microsome activities and species differences.” Xenobiotica, 33(2): 169-180.

  • Day R. M., Thalhauser, C.J., et al. (2003). “Tautomerism, acid-base equilibria, and H-bonding of the six histidines in subtilisin BPN’ by NMR”. Protein Science, 12: 794-810.

  • Lai, J.H., Zhou, Y., et al. (2003). “Microscopic acid-base equilibra of alanyl-boroAlanine.” Adv. Exp. Med. Biol., 524:333-338.

  • Sudmeier, J.L., Bradshaw, E.M., et al. (2003). “Identification of histidine tautomers in proteins by 2D 1H/13C(.delta.2) one-bond correlated NMR.” J. Am. Chem. Soc., 125(28): 8430-8431.

  • Rosay, M., Lansing, J.C., et al. (2003). “High-frequency dynamic nuclear polarization in MAS spectra of membrane and soluble proteins.” J. Am. Chem. Soc., 125(45): 13626-13627.

  • Ivanov, D., Bachovchin, W. W., et al. (2002). “Boron-11 Pure Quadrupole Resonance Investigation of Peptide Boronic Acid Inhibitors Bound to alpha-Lytic Protease.” Biochemistry 41(5): 1587-1590.

  • Bachovchin, W. W. (2001). “Contributions of NMR spectroscopy to the study of hydrogen bonds in serine protease active sites.” Magn. Reson. in Chem. 39 (Spec. Issue): S199-213.

  • Zhao, X., Sudmeier, J.L., et al. (2001). “Measurement of NH bond lengths by fast magic-angle spinning solid-state NMR spectroscopy: A new method for the quantification of hydrogen bonds.” J. Am. Chem. Soc. 123(44): 11097-11098.

  • Ash, E.L., Sudmeier, J.L., et al. (2000). “Unusual 1H NMR chemical shifts support (His) C.epsilon.1-H...O=C H-bond: proposal for reaction-driven ring flip mechanism in serine protease catalysis.” Proc. Natl. Acad. Sci. USA. 97(19): 10371-10376. Full Text.

  • Ash, E.L., Sudmeier, J.L., et al. (1997). “A low-barrier hydrogen bond in the catalytic triad of serine proteases? Theory versus experiment.” Science (Washington, D.C.). 278(5340): 1128-1132.

  • O'Connell, T.P., Day, R.M., et al. (1997). “A 13C-NMR study of the role of Asn-155 in stabilizing the oxyanion of a subtilisin tetrahedral adduct.” Biochem. J. 326(3): 861-866.

  • Freedman, S.J., Sanford, D.G., et al. (1996). “Structure and function of the epidermal growth factor domain of P-selectin.” Biochemistry 35(43): 13733-13744.

  • Guenther, U.L., Liu, Y., et al. (1996). “NMR analysis of interactions of a phosphatidylinositol 3'-kinase SH2 domain with phosphotyrosine peptides reveals interdependence of major binding sites.” Biochemistry 35(48): 15570-15581.

  • Luo, X., D.G. Sanford, et al. (1996). “Solution structure of the origin DNA-binding domain of SV40 T-antigen.” Nat. Struct. Biol. 3(12): 1034-1039.

  • Schmitz, T., Underwood, R., et al. (1996). “Potentiation of the immune response in HIV-1+ individuals.” J. Clin. Invest. 97(6): 1545-1549.

  • Sudmeier, J.L., Ash, E.L., et al. (1996). “HCN, a triple-resonance NMR technique for selective observation of histidine and tryptophan side chains in 13C/15N-labeled proteins.” J. Magn. Reson., Ser. B 113(3): 236-247.

  • Sudmeier, J.L., Guenther, U.L., et al. (1996). “Sensitivity optimization in continuous-flow FTNMR.” J. Magn. Reson., Ser. A 118(2): 145-156.

  • Tsilikounas, E., Rao, T., et al. (1996). “15N and 1H NMR Spectroscopy of the Catalytic Histidine in Chloromethyl Ketone-Inhibited Complexes of Serine Proteases.” Biochemistry 35(7): 2437-2444.

  • Yamaguchi, N., Plant, C., et al. (1996). “In vivo modulation of CD26 (dipeptidyl peptidase IV) in the mouse: Effects of polyreactive and monoreactive antibodies.” Transplantation 62(7): 973-985.

  • Guenther, U.L., Sudmeier, J.L., et al. (1995). “NOE enhancement in continuous-flow 13C and 15N FT NMR using upstream 1H preirradiation.” J. Magn. Reson., Ser. A 117(1): 73-77.

  • Silks, L.A. III, Dunkle, E., et al. (1995). “A reinvestigation of the synthesis of [15N2]hydroxymethylimidazole: useful in an improved synthesis of (D,L)-[tau,pi-15N2]histidine.” J. Labelled Compd. Radiopharm. 36(10): 947-951.

  • Snow, R. J. and Bachovchin, W. W. (1995). “Boronic acid inhibitors of dipeptidyl peptidase IV: A new class of immunosuppressive agents.” Adv. Med. Chem. 3: 149-177.

Issued Patents:

  • # 4,935,493: “Protease Inhibitors.” Inventors W. Bachovchin, G. Flentke, A. Plaut. Issued 6/19/90.

  • # 5,462,928: "Inhibitors of Dipeptidyl aminopeptidase type IV.” Inventors W. Bachovchin, G. Flentke, A. Plaut. Issued 10/31/95

  • # 5,580,979: “Phosphotyrosine peptidomimetics for inhibiting SH2 domain interactions.” Inventor W. Bachovchin Issued 12/3/96.

  • # 5,776,902: “Boronophenyl analogs of phosphotyrosines.” Inventor W. Bachovchin Issued 7/7/98.

  • # 5,965,532: “Multivalent compounds for crosslinking receptors and use thereof.” Inventor W. Bachovchin. Issued 10/12/99.

  • # 6,258,597: “Stimultion of Hematopoietic cells in vitro.” Inventors W. Bachovchin and B. Wallner. Issued 7/10/2001.

  • # 6,703,238: Methods of expanding antigen specific T cells. Issued 03/09/04.

  • # 6,803,357: Method of regulating glucose metabolish, and reagents related thereto. Issued 10/12/04.

  • # 6,825,169: Inhibitors of dipeptidyl-aminopeptidase type IV. Issued 11/30/04.

 


             

Sackler Home