Accession Number:

ADA371255

Title:

Sequence-Specific and Synergistic Binding of Drugs to DNA

Descriptive Note:

Annual rept. 23 Sep 97-22 Sep 98,

Corporate Author:

TENNESSEE STATE UNIV NASHVILLE

Personal Author(s):

Report Date:

1998-10-01

Pagination or Media Count:

18.0

Abstract:

Our goals were to study the sequence specific and synergistic binding of three drugs having distinctly different binding modes actinomycin D ACTD, an intercalator with GpC sequence preference chromomycin A3 CHR, a guanine specific minor groove binder and distamycin A DST, an A.T specific minor groove binder. Binding characteristics such as binding strength, sequence specificity, and kinetic behaviors of individual drug have earlier been investigated. These results formed the bases for designing suitable sequences for the synergistic binding study commenced during the past year. Oligomers of the form dATATA-XGCY-TATAT were chosen for the purpose, where X A, T, G, or C and Y is complementary to X. The choice was based on the findings that both ACTD and CHR prefer certain XGCY sites and DST binds strongly to the 5-base ATATA with a 21 binding mode. Binding titrations and kinetic measurements were made with ACTD in the absence or in the presence of DST and with DST in the absence or in the presence of ACTD. Initial results indicate some interference between ACTD and DST binding to these oligomers, especially on ACTD binding to DST-bound TGCA- and AGCT-containing oligomers. Further studies will be made with more suitable oligomeric sequences.

Subject Categories:

  • Medicine and Medical Research
  • Pharmacology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE