Application of circular dichroism to the study of interactions between small molecular compounds and DNA / 药学学报

Circular dichroism (CD) is an useful technique for monitoring DNA conformation changes resulting from changes in environmental conditions, such as temperature, ionic strength, and pH, and also for the study of the interaction between DNA and ligands (including small molecules and proteins). CD spectroscopy of DNA arises from the asymmetric backbone sugars and by the helical structures often adopted by nucleic acids. By the interpretation of induced circular dichroism (ICD) of ligand signals resulting from the coupling of electric transition moments of the ligand, DNA bases within the asymmetric DNA environment, ligand-DNA interactions, as well as the DNA-binding mode can be assessed. A number of important conclusions have been reported that related to the observed ICD signals resulting from the interactions between intercalators and groove binders with DNA. If short oligonucleotide sequences are used in the study, sequences-specific of binding also can be deduced. CD determination requires smaller amounts of sample, and not limited by the molecular weight or size and can be performed rapidly; though CD is of low resolution, but it's a complement to NMR and X-ray diffraction methods. This review will introduce the characters of the CD spectra of DNA, and its application to the studies of DNA with small molecules; some progress of the studies in our laboratory will also be discussed. CD is expected to be used as a screening method in seeking more DNA-targeted drugs, such as, antineoplastic, antimicrobial and antiviral drugs.

Three different drug interaction mathematical models used to evaluate the cytotoxicity of SAHA and arsenic trioxide in combination / 药学学报

To clarify the source of deviations of drug combination effects evaluated with different drug interaction mathematical models, the cytotoxicity of SAHA and arsenic trioxide and their combinations were observed in a series of human cancer cell lines and a normal cell line. The combined effects were evaluated with three drug interaction models: Loewe Additivity (LA), Bliss Independence (BI) and Chou's Median Effect Model. The evaluations with three different models were further compared with each other. We demonstrated that when dose-response curves were fitted with the same method, similar evaluated results for drug combinations would be derived with different models. The deviations of evaluated effects of drug combinations were attributed to different curve fitting methods used rather than the models themselves. The effects of drug combinations showed discrepancies on different cell lines, and at different combined drug concentrations on same cell line.