Michio Kurosu
Assistant Professor
Organic Synthesis/Medicinal Chemistry/Bioorganic Chemistry
Phone: 491-7628
Fax: 491-1815
Email:
Michio.Kurosu@Colostate.Edu
Office: B301A Microbiology Building
Lab: B305 Microbiology Building
Education
Research Fellow, Harvard University
Ph.D., Osaka University
M.Sc., Osaka University
B.Sc., Tokyo University of Pharmacy and Life Science
Research Interests
Synthesis and Biological Evaluation of Biologically Active Natural Products, Rational drug design, bioorganic chemistry, Development of Enzymatic Assays of Small Molecules, and New Chemical Tools.
Rational Drug-lead Design
Target Selection & Validation
We are working primarily on MDR-TB and MDR-Gram-positive drug targets whose 3D structures have not been previously determined. We are interested in electron transport associated proteins, glycosyltrasferases, fatty acid synthease, peptidoglycan synthease, and kinases.
Lead Generation
Based on (hypothetical) biosynthetic intermediates we design lead compounds for target proteins. We try to eliminate possible cross-reactivates against off-target proteins at early stage of drug discovery. We use a variety of lead generation techniques, including scaffold-based chemical screening, and a computational technique known as virtual ligand screening with closely related target proteins that have been characterized by X-ray crystallography.
Lead Optimization
Generation of small optimized library is our foundation for optimizing lead compounds. We typically deliver 100-150 molecules on polymer-support or in solution.
Natural Product Synthesis
We are interested in the development of efficient synthesis of biologically active natural products which are difficulty in obtaining enough amounts for in vivo assay. We are primary interested in anti-infective or anti-cancer natural products.
Bioorganic Chemistry
We are interested in unusual biological transformation found in bacterial system. We are currently elucidating a formal decarboxylative carbon-aromatic bond forming reaction found in the electron transport systems.
Development of Polymer-supported Chemistries
We are developing novel linkers for polymer-supported chemistries. Novel linkers possessing appropriate spacers are indispensable for generating library molecules efficiently. We are currently demonstrating our linkers in the syntheses of lipid I and II, and their analogues.
Recent Patents
Menaquine A Inhibitors, Kurosu, M.; Crick, D. C. US Patent 2007 pending.
A New Linker for Solid-Phase Organic Synthesis, Kurosu, M.; Crick, D. C. US Provisional Patent Application, 2007.
Book Chapters
Linker Strategies in Solid-Phase Organic Synthesis, John Wiley and Sons, Ltd, 2009
Selected Publications
Pub Med for Kurosu M.
Concise Synthesis of Capuramycin. Kurosu, M.; Li, K.; Crick, D. C. Org. Lett. 2009,11, 2393.
New Chiral Derivatizing Agents: Convenient Determination of Absolute Determination of Free Amino Acids by 1H-NMR, Kurosu, M.; Li, K. Org. Lett. 2009, 11, 911.
MenA Is a Promising Drug Target for Developing Novel lead Molecules to Combat Mycobacterium tuberculosis, Kurosu, M.; Crick, D. C. Medicinal Chemistry 2009, 5, 197.
(2,6-Dichloro-4-alkoxyphenyl)(2,4-dichlorophenyl)methyl Trichloroacetimidates: Reagents for Protections of Alcohols and Carboxylic acids in Solution or on Polymer-support, Kurosu, M.; Li, K. Synthesis 2009 in press.
Multiple-delayed Release Formulation Approach for the treatment of Methicillin-resistant Staphylococcus aureus. Kurosu, M. Expert Opinion Patent Evaluation 2008, 18, 1313.
Highly Efficient O-Glycosylations with p-Tolyl thioriboside and p-TolSOTf. Kurosu, M.; Li, K. J. Org. Chem. 2008, 73, 9767.
Synthetic Studies on Mycobacterium tuberculosis Specific Fluorescent Park’s Nucleotide Probe. Li, K.; Kurosu, M. Heterocycles 2008, 76, 455.
Discovery of 1,4-Dihydroxy-2-naphthoate Prenyltransferase Inhibitors: New Drug Leads for Multidrug-Resistant Gram-Positive Pathogens. Kurosu, M.; Narayanasamy, P.; Biswas, K.; Dhiman, R.; Crick, D. C. J. Med. Chem. 2007, 50, 3973.
Polymer-Supported (2,6-Dichloro-4-alkoxyphenyl)(2,4-dichlorophenyl)methanol: A New Linker for Solid-Phase Organic Synthesis, Kurosu, M.; Biswas, K.; Crick, D. C. Org. Lett. 2007, 9, 1141.
Chemoenzymatic Synthesis of Park's Nucleotide: Towards the Development of High-throughput Screening for MraY Inhibitors, Kurosu, M.; Mahapatra, S.; Narayanasamy, P.; Crick, D. C. Tetrahedron Lett. 2007, 48, 799.
Ganglioside GM3 Derivatives with Truncated Ceramide Moiety: Facial Synthesis and Inhibitiory Activity Against KB Cell Growth, Kurosu, M.; Kitagawa, I. J. Carbohydrate.Chem. 2006, 25, 427.
Small-Molecule Microarrays: Development of Novel Linkers and an Efficient Detection Method for Bound Proteins, Kurosu, M.; Mowers, W. A. Bioorganic & Medicinal Chemistry Letters 2006, 16, 3392.
Fe/Cr-and Co/Cr Mediated catalytic Asymmetric 2-Haloallylations of Aldehydes, Kurosu, M.; Lin, M-H.; Kishi, Y, J. Am. Chem. Soc. 2004, 126, 12248.
Studies on the Total Synthesis of Batrachotoxin, Kurosu, M; Kishi, Y, Review: Yuki Gosei Kagaku Kyokaishi 2004, 62, 1205
An Efficient Synthesis of Indane-Derived Bis(Oxazoline) and its Application to Hetero Diels-Alder Reaction on Polymer Support, Kurosu, M; Porter, J. R; Foley, M. A. Tetrahedron Lett. 2004, 45, 145.
Highly Diastereofacial Anti-Aldol Reaction: Practical Synthesis of Optically Active anti-2-Alkyl-3-Hydroxycarboxylic Acid Ester Units, Kurosu, M.; Lorca, M. J. Org. Chem. 2001, 66, 1205.
Selective Reduction of Aldehydes via BINOL-Zr Complex, Kurosu, M.; Lorca, M.; Kuhn D. Tetrahedron Lett. 2001, 42, 6243.
A Practical Synthesis of the Lipophilic Side Chain of the Polyoxypeptins, Lorca, M. Kurosu, M. Tetrahedron Lett. 2001, 42, 2431.
Expeditious Amide-Forming Reactions Using Thiol Esters, Kurosu, M. Tetrahedron Lett. 2000 41, 591.
Total Synthesis of (±)-Batrachotoxinin A, Kurosu, M.; Marcin, L. R.; Grinsteiner, T. J.; Kishi. Y. J. Am. Chem. Soc. 1998, 120, 6627.