Accession Number:

ADA374719

Title:

Crystallization, X-ray Structure Detemination and Structure-Based Drug Design for Targeted Malarial Enzymes.

Descriptive Note:

Annual rept. 15 Jun 98-14 Jun 99

Corporate Author:

ARMY MEDICAL RESEARCH AND MATERIEL COMMAND FORT DETRICK MD

Personal Author(s):

Report Date:

1999-07-01

Pagination or Media Count:

9.0

Abstract:

We have successfully expressed at least six recombinant proteins of the Plasm odium falciparum. We have crystallized and determined the structure of two of these proteins, the lactate dehydrogenase LDH and Rab6GTPase. Failure to crystallize other proteins was mostly due to lack of reproducibility in the expression of recombinant proteins. The most important accomplishment came from a collaboration with scientists from WRAIR. We were able to selectively inhibit the P. falciparum LDH in erythrocyte culture without severely affecting the host cells. Our ability to produce sufficient quantities of the active recombinant enzyme and success with obtaining high quality crystals of LDH, encouraged ArQule Inc. to select P. falciparum LDH as a target for developing specific antimalarial agent. According to the agreement between ArQule and us, high throughput screening of ArQule s combinatorial library will be conducted in collaboration with the company. For this purpose, we have adapted an enzyme assay for high throughput screening.

Subject Categories:

  • Medical Facilities, Equipment and Supplies
  • Microbiology
  • Pharmacology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE