Accession Number : ADA321901

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

Descriptive Note : Annual rept. 23 Sep 95-22 Sep 96,

Corporate Author : TENNESSEE STATE UNIV NASHVILLE

Personal Author(s) : Chen, Fu-Ming

PDF Url : ADA321901

Report Date : OCT 1996

Pagination or Media Count : 14

Abstract : Proposal was made 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 (CHR), 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 CHR and its sequence specificity at the tetranucleotide level. Comparative studies with self-complementary decamers of the form d(GTA-XGCY-TAC) suggest that CHR binds strongly to a 5tGC3F site but the binding affinities and dissociation kinetic behaviors are greatly affected by the adjacent base pairs. For example, the CHR binding affinity and the dissociation rate at the - GOCC- site are an order of magnitude stronger and slower than those at the -AGCT- site. Studies were also extended to include non-self-complementary tetranucleotide -XGCY- sequences with decamers of the form d(GTA-XGCY-ATG)/d(CAT-Y'GCX'-TAC), where X' and Y' are complementary to X and Y, respectively. Again significant modulation by the adjacent base pairs on the binding and kinetic behaviors are seen.

Descriptors :   *DEOXYRIBONUCLEIC ACIDS, *DRUGS, *CHEMOTHERAPY, *BREAST CANCER, SEQUENCES, BEHAVIOR, KINETICS, BINDERS, MODULATION, GROOVING, DISSOCIATION, SYNERGISM, GUANINE.

Subject Categories : Biochemistry
      Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE