Accession Number : ADA306436

Title :   Sequence-Specific and Synergistic Binding of Drugs to DNA.

Descriptive Note : Annual rept. 23 Sep 94-22 Sep 95,

Corporate Author : TENNESSEE STATE UNIV NASHVILLE

Personal Author(s) : Chen, Fu-Ming

PDF Url : ADA306436

Report Date : OCT 1995

Pagination or Media Count : 48

Abstract : We had proposed to study the sequence specific binding and synergistic effect of three drugs having distinctly different binding modes: actinomycin D (ACTD), a guanine specific intercalator; chromomycin A3, a guanine specific minor groove binder; and distamycin A, an A.T specific groove binder. To investigate the possible synergistic effects of drugs on DNA binding, it is essential that binding characteristics of each individual drug such as binding affinities, sequence specificities, and kinetic behaviors be well understood. During the past year, our laboratory has focused mainly on the detailed studies of ACTD. Comparative studies with dodecamers of the form d(AAAA-XGCX-TTTT) suggest that ACTD binds strongly to a 5'GC3' site with flanking T / T or C / C mismatches but weakly to that with G / G or A / A mismatches. In our binding studies with hairpins, it was found that this drug binds strongly to GpC- as well as some non-GpC-containing stems. We have also investigated the origin of its strong binding to a non-GC-containing octamer d(CGTCGACG) and concluded that it most likely is the consequence of end-stacking. During this period, we have also uncovered an interesting phenomenon of K+-induced supramolecular assembly of G-quadruplexes in d(CGG)4 which is inhibited by ACTD binding.

Descriptors :   *DEOXYRIBONUCLEIC ACIDS, *SEQUENCES, *DRUGS, *MAMMARY GLANDS, *BREAST CANCER, BEHAVIOR, KINETICS, BINDERS, GROOVING, SYNERGISM, ACTINOMYCES, GUANINE.

Subject Categories : Pharmacology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE