# ENZYMES OF FOLATE METABOLISM IN PROTOZOA--LEISHMANIA

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1990 · $205,794

## Abstract

This proposal involves a multi-disciplinary research effort
directed at studies of a) enzymes in folate metabolism in protozoa
and b) mechanisms of drug resistance in these organisms.  The
organisms to be studied are Leishmania and Plasmodium, casual
agents of diseases (Leishmaniasis and malaria, respectively) of
worldwide importance.  Our objectives are aimed at obtaining
fundamental biochemical information, with the belief that such
knowledge will provide insight into how to exploit what is found
and assist in controlling these organisms.

We will continue studies on the structure, function and inhibition
of the bifunctional thymidylate synthase (TS)-dihydrofolate
reductase (DHFR) which is uniquely found in protozoa.  We intend
to express the enzyme from Leishmania, and study its higher
order structure in detail; studies on computer assisted structure
modeling and drug design will be initiated.  We will continue
studies on the amplified DNA found in anti-folate resistant
Leishmania.  We will further characterize the structure of these
DNAs and delineate differences observed in different cell lines.
In Plasmodium falciparum, we will isolate the TS-DHFR gene,
characterize it and express it in E. coli or yeast; we will study
molecular aspects of drug resistance towards anti-folates and
initiate other studies of enzymes in folate metabolism.

## Key facts

- **NIH application ID:** 3128740
- **Project number:** 5R01AI019358-09
- **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:** 1990
- **Award amount:** $205,794
- **Award type:** 5
- **Project period:** 1982-09-01 → 1992-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3128740

## Citation

> US National Institutes of Health, RePORTER application 3128740, ENZYMES OF FOLATE METABOLISM IN PROTOZOA--LEISHMANIA (5R01AI019358-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3128740. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*