# EXPERIMENTAL STUDIES OF DRUG-NUCLEIC ACID INTERACTIONS

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1994 · $176,951

## Abstract

Chemotherapy is an important tool in the clinical management of
cancer.  The long-term objective of the research proposed here is
to elucidate the structure and dynamics of anticancer drug-DNA
complexes in order to enhance our understanding of their
mechanism of action and our ability to design new, more effective
drugs.  In order to achieve this objective, we propose to apply a
variety of spectroscopic techniques to the analysis of drug-DNA
interactions.  The principal tool proposed for structural
investigation is high resolution proton NMR in one and two
dimensions.  We plan to study the oligonucleotide complexes of
several different antitumor antibiotics, including chromomycin
and its analogs mithramycin and olivomycin, along with
actinomycin and nogalomycin.  We will be investigating the
structure and sequence specificity of these drug-DNA complexes
using one dimensional experiments and two dimensional COSY,
HOHAHA and NOESY experiments.  Results will be analyzed by a
combination of computer graphics, complete relaxation matrix
analysis, energy minimization, and distance geometry.  In addition
to standard DNA duplexes, we will examine the effects of DNA
modification, such as methylation, on the structure of these
complexes.  Finally, the proposed structural studies based on NMR
methods will be complemented by equilibrium and kinetic binding
studies to provide a thermodynamic framework for their
interpretation.

## Key facts

- **NIH application ID:** 2190324
- **Project number:** 9R01GM051650-14
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **SAM.gov UEI:** KMH5K9V7S518
- **Principal Investigator:** RICHARD H SHAFER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $176,951
- **Award type:** 9
- **Project period:** 1980-07-01 → 1996-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2190324

## Citation

> US National Institutes of Health, RePORTER application 2190324, EXPERIMENTAL STUDIES OF DRUG-NUCLEIC ACID INTERACTIONS (9R01GM051650-14). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2190324. Licensed CC0.

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