# POLY-Y-GLUTAMATION AND ANTITUMOR ACTIVITY OF ANTIFOLATES

> **NIH NIH R01** · UNIVERSITY OF SOUTH ALABAMA · 1989 · $92,018

## Abstract

We propose to test the hypothesis whether the superior antitumor activity
exhibited by the experimental drug 10-deazaaminopterin (10-DA) compared to
methotrexate (MTX) in several responsive tumors is due to the differences
in its ability to undergo metabolism to the poly-Gamma-glutamates.
Therefore, a comparative study of the metabolism of 10-DA and MTX will be
undertaken to evaluate the relationship between poly-Gamma-glutamation and
antitumor activity.  These studies will include the biosynthesis, turnover
and chemical characterization of these metabolites in mice.  A comparative
study of the metabolism of both drugs to their poly-Gamma-glutamates will
also be undertaken in mice inoculated with the ascitic form of L-1210
leukemia, and the relative accumulation and persistence of these
metabolites in the tumor versus the normal drug limiting proliferative
tissues will be examined.  Our long range objective is to use the
information thus obtained to design analogs of 10-DA and MTX which will
have altered abilities of poly-Gamma-glutamation; changes which might
contribute to the development of more effective anticancer drugs.  To aid
in these studies 14C-labeled 10-DA and both labeled and unlabeled authentic
poly-Gamma-glutamates of 10-DA will be synthetized.  As an alternative to
the solid phase and classifical solution phase syntheses of the
poly-Gamma-glutamyl derivatives, we propose the "solution phase synthesis"
for the preparation of these metabolites which we believe will eiminate the
undesirable features of both the existing methods.

## Key facts

- **NIH application ID:** 3170561
- **Project number:** 5R01CA032687-06
- **Recipient organization:** UNIVERSITY OF SOUTH ALABAMA
- **SAM.gov UEI:** QB12VPNQQFE8
- **Principal Investigator:** MADHAVAN P. NAIR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $92,018
- **Award type:** 5
- **Project period:** 1983-06-01 → 1990-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3170561

## Citation

> US National Institutes of Health, RePORTER application 3170561, POLY-Y-GLUTAMATION AND ANTITUMOR ACTIVITY OF ANTIFOLATES (5R01CA032687-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3170561. Licensed CC0.

---

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