# PURINE/PYRIMIDINE METABOLISM IN TRICHOMONAS AND GIARDIA

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1988 · $213,429

## Abstract

Three anaerobic protozoan parasites, Giardia Lamblia, Trichomonas vaginalis
and Tritrichomonas foetus, which all grow naturally by adhering to host
epithelial cells and performing phagocytosis, have been found lacking the
capability of de novo synthesis of purine and pyrimidine nucleotides and
deficient in dihydrofolate reductase and thymidylate synthetase
activities.  They depend on rather simple salvage pathways for purines,
pyrimidines and nucleosides.  These pathways, delineated by us during the
past two years, have presented several pivotal enzymes which not only are
essential for survival of these parasites but also exhibit unique substrate
specificities qualifying themselves as potential targets of antiparasitic
chemotherapy.  These enzymes are the APRT, GPRT and UPRT in G. lamblia,
HXGPRT, UPRT and IMPDH in T. foetus and the deoxyribonucleoside
phosphotransferase of T. vaginalis.  The GPRT, HXGPRT and IMPDH have been
purified to homogeneity and shown to have many different properties from
the related host enzymes.  We are planning on a screening program for
inhibitors of these isolate enzymes as one way of finding chemotherapeutic
agents.  On the other hand we will prepare pure samples of G. lamblia GPRT,
T. foetus HXGPRT, T. foetus IMPDH and mouse sarcoma 180 IMPDH in microgram
quantities by the established procedures.  The N-terminal sequences of the
four purified enzymes will be determined, the corresponding
oligonucleotides will be synthesized and used as probes to begin
identifications, clonings and sequencings of the genes encoding these
enzymes for sequence comparisons.  It is anticipated that sequence
differences associated with the enzyme active sites may explain the
different substrate specificities and help new drug designs.  Meanwhile,
further purifications of the UPRT's and the T. vaginalis
deoxyribonucleoside phosphotransferase will be pursued with affinity column
chromatographies.  An exciting observation of the presence of a
double-stranded RNA in T. vaginalis, the discovery of the RNA gene in T.
vaginalis DNA and the possible relationship between the RNA and the
metronidazole-sensitivity of T. vaginalis will lead us into further pursue
of these new findings.  Genomic libraries of T. vaginalis will be
established and the double-stranded RNA will be used as a probe to initiate
the identification, cloning and sequence determination of its encoding
genome for further understanding of the biological function of the
double-stranded RNA.

## Key facts

- **NIH application ID:** 3128773
- **Project number:** 5R01AI019391-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **SAM.gov UEI:** KMH5K9V7S518
- **Principal Investigator:** Ching Chung WANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $213,429
- **Award type:** 5
- **Project period:** 1982-08-01 → 1990-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3128773

## Citation

> US National Institutes of Health, RePORTER application 3128773, PURINE/PYRIMIDINE METABOLISM IN TRICHOMONAS AND GIARDIA (5R01AI019391-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3128773. Licensed CC0.

---

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