Method to identify specific inhibitors of IMP dehydrogenase

Details Method to identify specific inhibitors of IMP dehydrogenase Method to identify specific inhibitors of IMP dehydrogenase

1997-12-24

2000-11-28

Achutamurthy, Ponnathapu

Chemistry: molecular biology and microbiology

Measuring or testing process involving enzymes or...

Involving oxidoreductase

435190, 43525231, 43525232, 4352544, 435325, C12Q 132, C12N 904, C12N 120, C12N 500

Patent

active

06153398&

ABSTRACT:
This invention relates to methods to identify specific inhibitors of the purine nucleotide synthesis enzyme, IMP dehydrogenase (IMPDH). IMPDH is an essential enzyme found in all free-living organisms from humans to bacteria and is an important therapeutic target. The invention allows the identification of specific inhibitors of any IMPDH enzyme which can be expressed in a functional form in a recombinant host cell. A variety of eukaryotic or prokaryotic host systems commonly used for the expression of recombinant proteins are suitable for the practice of the invention. The methods are amenable to high throughput systems for the screening of inhibitors generated by combinatorial chemistry or other methods such as antisense molecule production. Utilization of exogenous guanosine as a control component of the methods allows for the identification of inhibitors specific for IMPDH rather than other causes of decreased cell proliferation.

REFERENCES:
patent: 5314813 (1994-05-01), Peterson et al.
Carr, SF et al. (1993). "Characterization of Human Type I and Type II IMP Dehydrogenases." Journal of Biological Chemistry. 268(36): 27286-27290.
Amman, E. et al., Gene, vol. 69, pp. 301-315, 1988.
Kim, B. et al., Proc. Natl. Acad. USA, vol. 92, pp. 684-688, Jan. 1995.
Ashbaugh, C. et al., Gene, vol. 165, pp. 57-60, 1995.
Ashbaugh, C. et al., Genbank, Accession No. U26056, Jul. 1996.

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