User:Michael P. Pollastri
From OpenWetWare
Contents |
Research interests - Medicinal Chemistry
My research interests primarily revolve around the development of novel probe compounds that may be utilized for validation of molecular targets for therapeutic intervention. While RNAi is undoubtedly a powerful tool in elucidating biological function of targets, the druggability of the target is most readily confirmed by the actual development of small molecules that potently and selectively perturb the function of these targets, and that display physicochemical properties that will allow in vivo validation of the target and mechanism.
While we will undertake a wide variety of these types of projects, the centerpiece of our research efforts is the validation of molecular targets that are relevant for neglected tropical diseases such as African sleeping sickness or Chagas disease, ailments that are caused by the trypanosome parasites. In prosecuting these targets we intend to:
- Identify key molecular targets for small molecule intervention and validate their relevance for therapies
- Evolve the chemical matter for these targets to the point where their properties profiles are amenable to pre-clinical assessment and hand-off to industrial or not-for-profit collaborators for further development
- Demonstrate the power of a "distributed research network", wherein the many different components of a highly complex biopharmaceutical research effort are utilized from various institutions. These components include computational chemistry, bioinformatics, disease biology, protein science, structural biology, parasitology, and systems biology.
Target ID by Parachute. Our overarching strategy for target identification is to use bioinformatic techniques to uncover targets in the parasite that have close human homologues that have been previously pursued by the biopharmaceutical research community. In that way, we hope to use the information developed in the context of these biopharma projects to rapidly prosecute the newly-identified parasitic targets. For example, a number of phosphodiesterase enzymes have been identified and characterized in trypanosomes. These enzymes have moderate sequence homology to human PDEs, which are well-established and deeply-studied targets for human disease. Our expectation is that we can readily transfer the knowledge of human PDE medicinal chemistry into rapid development of trypanosomal PDE inhibitors.
The Medicinal Chemistry & Core Synthesis Facility. I serve as the director of the Medicinal Chemistry & Core Synthesis Facility at Boston University (MCCSF-BU). This core facility collaborates on a fee-for-service basis with biomedical researchers at the University and in the local biopharmaceutical environment. Our facility performs synthesis of known compounds and standards, preparation of small compound analog arrays, development of fluorescent probe compounds, and provides medicinal chemistry consulting resource.
Contact Info
Michael P. Pollastri, PhD
Research Assistant Professor
Boston University Department of Chemistry
590 Commonwealth Avenue
Boston, MA 02215
Education
- 2004, PhD, Brown University
- 1998, MS, Duke University
- 1995, AB, College of the Holy Cross
Industry experience
Pfizer Global Research & Development – Cambridge, MA Laboratories
- Principal Scientist - Head of Chemical Technologies – (2005-2007)
- Senior Scientist – Medicinal Chemistry – (2003-2005)
Pfizer Global Research & Development – Groton, CT Laboratories
- Associate Scientist, Medicinal Chemistry – (2003)
- Assistant Scientist, Medicinal Chemistry – (1998-2003)
Publications
- Pollastri, M. P. “Development of continuous flow synthesis for production of compounds for medicinal chemistry”, ChemTracts—Org. Chem. 2008, in press.
- Bazin, M; Shi, H; Delaney, J.; Kline, B;, Zhu, Z.; Kuhn, C.; Berlioz, F.; Farley, K.; Fate, G.; Lam, W.; Walker, G.; Yu, L.; Pollastri, M.P. “Efficient use of the iron ortho-nitrophenylporphyrin chloride to mimic biological oxidations of dimethylaminoantipyrine”, Chem. Biol. Drug Design, 2007, 70, 354-359.
- Pollastri, M.P., Sagal, J.F., Chang, G., “The Conversion of Alcohols to Halides Using a Filterable Phosphine Source”, Tetrahedron Letters 2001, 35, 2459-2460.
- Pollastri, M.P., Porter, N.A., McIntosh, T.J., Simon, S.A., “Synthesis, Structure, and Thermal Properties of 1,2-Dipalmitoylgalloylglycerol (DPGG), A Novel Self-Adhering Lipid”, Chemistry and Physics of Lipids 2000, 104, 67-74.
- McIntosh, T.J., Pollastri, M.P., Porter, N.A., Simon, S.A, “Polyphenols increase adhesion between lipid bilayers by forming interbilayer bridges”, Basic Life Sci. 66(Plant Polyphenols 2) 1999, 451-470.
- Jones, P.B., Pollastri, M.P., Porter, N.A., “2-Benzoylbenzoic Acid: A Photolabile Mask for Alcohols and Thiols.” Journal of Organic Chemistry 1996, 61, 9455-9461.
- Curran, T.P., Pollastri, M.P., Abelleira, S.M., Messier, R.J., McCollum, T.A., Rowe, C.G., “Loss of the tert-Butyloxycarbonyl (Boc) Protecting Group Under Basic Conditions.” Tetrahedron Letters 1994, 35, 5409-5412.
- Curran, T.P., Smith, M.B., Pollastri, M.P., “Cis-3,5-Dimethyl-3,5-Piperdinedicarboxylic Acid, An Amino Diacid Variant of Kemp’s Triacid.” Tetrahedron Letters 1994, 35, 4515-4518.
Patents
- Chang, G., Didiuk, M. T. Finneman, J. I., Garigiapati, R. S., Kelley, R. M., Perry, D. A., Ruggeri, R. B., Bechle, B. M., Pollastri, M. P. “Preparation of 1,2,4-substituted-1,2,3,4-tetrahydro-and 1,2-dihydroquinoline and 1,2,3,4-tetrahydroquinoxaline derivatives as cetp inhibitors for the treatment of atherosclerosis and obesity. WO 2004085401.
Presentations
- Zhu, Z.; Shalaeva, M.; Pollastri, M.P.; Stanton, R.V. “Tautomer stability and pKa evaluation.” 234th ACS National Meeting, Boston, MA, 2007.
- Pollastri, M.P., Walters, E., Bazin, M., Otte, D.A., Nugent, R.A. “Developing New Chemical Technologies at the RTC – A PGRD Testing Ground”, 6th Pfizer Medicinal Chemistry Symposium, 2005.
- Pollastri, M. P., Otte, D. A., Wynn, T.A., Ding, Y.-H., Kohls, D., Low, S., Soulard, P., McLaughlin, M., Xi, H., Kuhn, C., Rennie, G., Springer, S., Johnson, T., Delaney, J., “Development of dynamic combinatorial chemistry as a novel hit-to-lead methodology”, 6th Pfizer Medicinal Chemistry Symposium, 2005.
- Pollastri, M. P., Otte, D. A., Wynn, T.A., Ding, Y.-H., Kohls, D., Low, S., Soulard, P., McLaughlin, M., Xi, H., Kuhn, C., Rennie, G., Springer, S., Johnson, T., Delaney, J., “Development of dynamic combinatorial chemistry as a novel hit-to-lead methodology”, Groton Chemistry Forum, Groton, CT, 2005
- Pollastri, M. P. “Microwave-mediated synthesis: A green chemistry technology.” 229th ACS National Meeting, San Diego, CA, 2005.
- Pollastri, M.P., Sagal, J.F., Chang, G., “Conversion of alcohols to halides using a filterable source of phenylphosphine.” 218th ACS National Meeting, New Orleans, LA, 1999.
- Curran, T.P., Pollastri, M.P., Abelleira, S.M., Messier, R.J., McCollum, T.A., Rowe, C.G., “Rearrangement of the tert-butyloxycarbonyl (Boc) Protecting Group Under Basic Conditions”209th National Conference of the American Chemical Society, San Diego, CA, 1994.
