# DNA BINDING OF ANTITUMOR DRUGS:  COMPUTER ANALYSIS

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 1987 · $74,794

## Abstract

The goals of this project are to model the binding of a selection of
antitumor drugs to double helical DNA using molecular mechanics
and computer graphics.  Where it is appropriate, attempts to
verify these models by physical measurements including 2D-
NOESY experiments will be undertaken.  The resulting models
should be valuable in understanding the mode of action of these
drugs and in the subsequent rational design of their analogs.

Specific aims are as follows.  1) Derive a binding model for
sibiromycin, a pyrrolo(1,4)benzodiazepine bearing an aminosugar.
Explore the use of molecular mechanics in explaining the
preference of neothramycin A for poly(dG) . poly(dC) over poly
(dGdC) . poly(dGdC).  2) Model the binding of saframycin A,
naphthyridinomycin, and quinocarcin, examples of three types of
drugs that appear to act by a similar process, groove binding
followed by alkylation.  Verify this binding process by 13C-NMR
and 2D-NMR experiments.  3) Evaluate the possibility that
streptonigrin is a groove binder by appropriate physical
measurements.  4) Develop a model for the intercalative binding
of ellipticene and important analogs.  Also model the binding of
the o-quinone derived from 9-hydroxyellipticene and see if it can
react with a nucleophile on the DNA while bound.  5) Investigate
the intercalation of leucanthone and analogs by deriving a
computer model and comparing it with the 2D-NMR spectrum of a
DNA complex.  Also, compare Tm measurements on DNA, free
and bound to these compounds, with calculated relative binding
strengths.

The 2D-NMR experiments will include NOESY and COSY
techniques to locate exact binding interactions between atoms in
the drugs and in the oligonucleotides d(ATGCAT)2 and
d(GCATATGC)2.  Other 1H-NMR experiments will include T2
measurements to probe structural and dynamic aspects of the
adducts and 1D-NOE measurements to assign adenine H(2) protons
in the oligonucleotides and their adducts.

## Key facts

- **NIH application ID:** 3175634
- **Project number:** 2R01CA037798-03
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **SAM.gov UEI:** ED44Y3W6P7B9
- **Principal Investigator:** WILLIAM A REMERS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $74,794
- **Award type:** 2
- **Project period:** 1985-08-01 → 1988-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175634

## Citation

> US National Institutes of Health, RePORTER application 3175634, DNA BINDING OF ANTITUMOR DRUGS:  COMPUTER ANALYSIS (2R01CA037798-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175634. Licensed CC0.

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