people
|Faculty
|Kazunori Koide
 |
Kazunori Koide Department of Chemistry |
Brief CV
1989 BS in Pharmaceutical Sciences, The University of Tokyo
Research supervisor: Masaji Ohno
1991 MS in Pharmaceutical Sciences, The University of Tokyo
Research supervisor: Masaji Ohno
1997 PhD in Chemistry, The University of California, San Diego
Research supervisor: K. C. Nicolaou
1997-2000 Postdoctoral fellow, Harvard University
Research supervisor: Gregory L. Verdine
Research program:
Our research program is aimed at developing chemical tools that are useful in biological research. We develop new synthetic methods and technologies to prepare these chemical tools.
Despite the rapid progress in biology in recent years, it remains difficult to elucidate the mechanisms of biological events in living cells mostly because there are few methods to regulate these events in intact cells. The regulation of a specific biological event by a cell-permeable small molecule in living cells will permit investigation of the target biomacromolecule in great detail. Furthermore, development of cell-permeable small molecules that will allow for measurement of kinetics and thermodynamics of biomacromolecules will help to elucidate the mechanisms of complex cellular events.
Total Syntheses and Biological Studies of Natural Products
We are currently studying FR901464, a natural product that regulates cancer-related genes by novel mechanisms. This compound inhibits cancer proliferation at concentrations as low as 1 nM. To study FR901464, we completed a chemical total synthesis of this natural product. Combination of this powerful, stereocontrolled chemical synthesis and cell biology will provide insights into the molecular mechanisms of FR901464. More recently, we have developed an exceptionally active FR901464 analog (meayamycin) that inhibits tumor growth at 10 pM (analoguous to one pack of sugar (5 grams) at a coffee shop in 400 Olymic swimming pools).
Increased thermotolerance associated with tumors is a major problem in cancer radiotherapy, and such tolerance is mediated by heat shock proteins. Therefore, inhibitors of heat shock proteins are of great interest in medicine. Stresgenin B is a densely functionalized natural product that inhibits heat shock proteins. We have developed a new conjugate addition reaction and are applying this method to synthesize stresgenin B.
Development of Fluorescent Sensors for Metals and Biomacromolecules
DNA transcription is the pivotal step in many cellular processes, and regulation of this complex biological event is essential for homeostasis. Currently available methods used to study this process do not enable real-time monitoring of DNA transcription in intact cells. To gain insights into the transient RNA levels of living cells in real-time, we are currently developing fluorescent sensors that visualize RNA.
Although palladium is widely used in synthetic organic chemistry and materials, it is known to be toxic. We have developed a fluorescent sensor that can detect palladium contaminated in drugs at 1 ppm level.
Diversity-Oriented Synthetic Methodology Development and Skeletally and Functionally Diverse Library Synthesis
Diversity-oriented organic synthesis provides new opportunities for methodology development. We have developed several new synthetic methods to diversify gamma-hydroxy-alpha, beta-acetylenic esters. Based on this chemistry, we are synthesizing skeletally diverse library compounds aimed at chemogenomic studies. Additionally, we developed new synthetic technology based on cross-olefin metathesis that allows for the synthesis of functionally diverse library compounds. Using this technology, highly functionalized library comopounds are being synthesized in our laboratory.
Awards
Thieme Chemistry Journals Award (2007), Merck Fellow of the Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation (1998-2000), Naito Foundation Fellowship (1991-1992)
Selected Publications
"Fluorescent sensors for specific RNA: A general paradigm using chemistry and combinatorial biology," B. A. Sparano, K. Koide, J. Am. Chem. Soc., 2007, 129, 4785–4794
"Total synthesis, fragmentation studies, and antitumor/antiproliferative activities of FR901464 and its low picomolar analogue," B. J. Albert, A. Sivaramakrishnan, T. Naka, N. L. Czaicki, K. Koide, J. Am. Chem. Soc., 2007, 129, 2648-2659
"Sodium Bicarbonate-Catalyzed Stereoselective Isomerizations of Electron-Deficient Propargylic Alcohols to (Z)-Enones," J. P. Sonye, K. Koide, J. Org. Chem., 2007, 72, 1846-1848
"Review: Total Syntheses of FR901464," K. Koide, B. J. Albert, J. Synth. Org. Chem., Jpn., 2007, 65, 119-126
"On the Mechanism of DABCO-Catalyzed Stereoselective Isomerization of gamma-Hydroxy-alpha,beta-Alkynoates to gamma-Oxo-alpha,beta-(E)-Alkenoates," J. P. Sonye, K. Koide, Org. Lett., 2006, 8, 199–202
"Total synthesis of FR901464, an antitumor agent that regulates the transcription of oncogenes and tumor suppressor genes," B. J. Albert, A. Sivaramakrishnan, T. Naka, K. Koide, J. Am. Chem. Soc., 2006, 128, 2792–2793
"A new paradigm for the development of fluorescent RNA imaging technology using synthetic molecules," K. Koide, Amer. Biotechnol. Lab. (Invited account), 2006, 24, 8–10
"Base-catalyzed stereoselective isomerization of electron-deficient propargylic alcohols to E-enones," J. P. Sonye, K. Koide, J. Org. Chem., 2006, 71, 6254–6257
"A strategy for the development of small molecule-based sensors that strongly fluoresce when bound to a specific RNA," B. A. Sparano, K. Koide, J. Am. Chem. Soc., 2005, 127, 14954–14955 (Ranked 6th in the Most-Accessed Articles: Oct-Dec, 2005)
"A mild method for the synthesis of gamma-hydroxy-alpha,beta-acetylenic esters," S. P. Shahi, K. Koide, Angew. Chem. Int. Ed., 2004, 43, 2525-2527