Accession Number : ADA337826

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

Descriptive Note : Annual rept. 23 Sep 96-22 Sep 97,

Corporate Author : TENNESSEE STATE UNIV NASHVILLE

Personal Author(s) : Chen, Fu-Ming

PDF Url : ADA337826

Report Date : OCT 1997

Pagination or Media Count : 15

Abstract : Combination chemotherapy is one of the important strategies in cancer treatments. This is based on the observation that administering certain drugs together is more effective than giving individual drugs separately. Although the reason for such an effect is not understood, it may be related to the synergistic effect of their binding to biomacromolecules. Consequently, studies on the interplay among drugs capable of binding to different regions of DNA will be of considerable interest. Understanding the synergism of drugs at the molecular level may have important implication for designing more effective chemotherapeutic strategies in breast cancer treatments. Our proposal focuses on 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 (DST), an AeT specific groove binder. In order 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 thoroughly elucidated. Consistent with the Statement of Work outlined in the proposal, our laboratory has focused on the sequence specificity and binding mode studies of DST during the past year.

Descriptors :   *DRUGS, *SYNERGISM, *BREAST CANCER, MOLECULAR STATES, OBSERVATION, DEOXYRIBONUCLEIC ACIDS, MACROMOLECULES, BEHAVIOR, KINETICS, GROOVING, CHEMOTHERAPY, CANCER, GUANINE.

Subject Categories : Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE