Christine Crane

 

PhD Student

Location:

HCI G-304

Phone:

+41-1-632 4501

e-mail:

Christine Crane

Education

1995-1999:

University of San Diego (San Diego, California, USA)
Bachelor of Arts in Biology
Bachelor of Arts in Chemistry

1999-2000:

Research Assistant, Trega Biosciences (La Jolla, California)

2000-2002:

Staff Scientist, Bristol-Myers Squibb Research Labs
(formerly Dupont Pharmaceuticals, La Jolla, California)

2002-present:

PhD with Prof. F. Diederich at ETH Zurich

Project

The non-mevalonate pathway, discovered by pioneering work of Rohmer, Arigoni and Sahm, is as an alternative biosynthestic pathway to the mevalonate pathway (a target for anticholestererolemia drugs) for the biosynthesis of the universal precursors to terpene natural products, isopentenylpyrophospahte (IPP) and dimethylallyldiphosphate (DMAPP) (Figure 1). It is exclusively operative in the plastids of higher and genes coding for enzymes in the pathway have been found in many organisms responsible for numerous problematic human diseases such as Plasmodium spp., H. influenzae, N. meningitidis, and M. tuberculosis. To date only two inhibitors of the pathway, Fosmidomycin (and analogues) and a breakdown product of Clomazone, have been identified (Figure 2). The former inhibits IspC and is currently under clinical evaluation for the treatment of malaria. The later is herbicidial compound, which inhibits DXS synthase (Figure 1b). The current thesis focuses on the struture-based design of inhibitors of the cyclodiphosphate synthase enzyme, IspF (in collaboration with Professor Adelbert Bacher and co-workers at the Thechnical University of Munich).

Figure 1: The non-mevalonate pathway for the biosynthesis of IPP and DMAPP.

Figure 2: Fosmidomycin and Clomazone, inhibitors of the non-mevalonate pathway.

Publications

V. Molteni, M. M. Hamilton, L. Mao, C. M. Crane, A. P. Termin, D. M. Wilson, Synthesis 2002, 1669-1674. Aqueous one-pot synthesis of pyrazoles, pyrimidines and isoxazoles promoted by microwave irradiation.

V. Molteni, J. Penzotti, D. M. Wilson, A. P. Termin, L. Mao, C. M. Crane, F. Hassman, T. Wang, H. Wong, K. J. Miller, S. Grossman, P. D. J. Grootenhuis, J. Med. Chem. 2004, 47, 2426-2429. N-Phenylphenylglycines as Novel Corticotropin Releasing Factor Receptor Antagonists.

C. M. Crane, J. Kaiser, N. L. Ramsden, S. Lauw, F. Rohdich, W. Eisenreich, W. N. Hunter, A. Bacher, F. Diederich, Angew. Chem. Int. Ed. 2006, 45, 1069-1074. Fluorescent inhibitors for IspF, an enzyme in the non-mevalonate pathway for isoprenoid biosynthesis and a potential target for antimalarial therapy.

last update: Mai 2006