# ENZYMES OF FOLATE METABOLISM IN PROTOZOA--LEISHMANIA

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1992 · $163,886

## Abstract

This proposal involves a multi-disciplinary research effort directed at
studies of enzymes in folate metabolism in protozoa, in particular the
bifunctional thymidylate synthase-dihydrofolate reductase (TS-DHFR).  The
sources to be studied are Leishmania, Trypanosoma and Plasmodium, casual
agents of diseases of worldwide importance (Leishmaniasis,
Trypanosomiasis and Malaria, respectively).  Our objectives are aimed at
obtaining fundamental biochemical information, with the belief that such
knowledge will provide insight into how to assist in controlling these
organisms and the diseases they cause.

We will continue studies on the structure, function and inhibition of the
bifunctional thymidylate synthase-dihydrofolate reductase (TS-DHFR) which
is uniquely found in protozoa.  We intend to express large amounts of the
enzymes and study their structures and functions in detail; studies on
molecular modeling and drug design will be performed.  In Plasmodium
falciparum, we will also prepare TS-DHFR genes from antifolate
drug-resistant mutants, express the gene products in E. coli or yeast,
and characterize them in detail.  We will study molecular aspects of drug
resistance towards antifolates to prove the molecular mechanisms of
antifolate-resistance, and hopefully obtain drugs which circumvent
resistance.

## Key facts

- **NIH application ID:** 3128735
- **Project number:** 2R01AI019358-11
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **SAM.gov UEI:** KMH5K9V7S518
- **Principal Investigator:** DANIEL V. SANTI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $163,886
- **Award type:** 2
- **Project period:** 1982-09-01 → 1997-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3128735

## Citation

> US National Institutes of Health, RePORTER application 3128735, ENZYMES OF FOLATE METABOLISM IN PROTOZOA--LEISHMANIA (2R01AI019358-11). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3128735. Licensed CC0.

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