# SPECIFICITY OF INTERCALATION REACTIONS

> **NIH NIH R01** · UNIVERSITY OF MISSISSIPPI MED CTR · 1993 · $102,595

## Abstract

The long-range objective of the proposed research is to understand the
molecular mechanisms that govern the sequence-specific DNA binding of
clinically useful intercalating antibiotics.  A quantitative DNase I
footprinting titration method will be used to identify the preferred DNA
binding sites of the anticancer anthracycline antibiotics (daunomycin,
adriamycin, nogalamycin) and the newly synthesized anthrapyrazole
antibiotics.  The method will further be used to estimate binding constants
for the interaction of these compounds with their preferred sites.  Once
the identity of these preferred sites is known, more detailed binding
studies using synthetic deoxyoligonucleotides of designed sequence will be
conducted, using the methods of absorbance and fluorescence spectroscopy,
titration calorimetry, and stopped-flow kinetics.  These studies will
provide a detailed thermodynamic and kinetic profile describing the
specific binding of intercalators to their preferred DNA sites, a
fundamental characterization that has heretofore been lacking.  This
information will complement existing structural data for the anthracycline
antibiotics obtained by x-ray diffraction, and should help identify the
molecular determinants of site specific binding by these compounds.
Further, these results should provide a critical test of the predictions
derived from molecular mechanics calculations concerning anthracycline
antibiotic sequence specificity.  Finally, the possible linkage between
sequence specific antibiotic binding and topoisomerase II inhibition will
be explored by DNase I footprinting methods.  All of the proposed studies
are logical extensions of what have been successful, productive and
cost-effective research efforts in our laboratory.  The results of these
studies should provide fundamental physical chemical data of possible use
in the rational design of new intercalating antibiotics targeted toward
specific DNA binding sites.

## Key facts

- **NIH application ID:** 3173231
- **Project number:** 5R01CA035635-08
- **Recipient organization:** UNIVERSITY OF MISSISSIPPI MED CTR
- **SAM.gov UEI:** X59NJBFL8BJ3
- **Principal Investigator:** Jonathan B. CHAIRES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $102,595
- **Award type:** 5
- **Project period:** 1984-03-01 → 1996-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173231

## Citation

> US National Institutes of Health, RePORTER application 3173231, SPECIFICITY OF INTERCALATION REACTIONS (5R01CA035635-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173231. Licensed CC0.

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