ATP hydrolysis fuels the ability of helicases and related proteins to translocate on nucleic acids and separate base pairs. As a consequence, nucleic acid binding stimulates the rate at which a helicase catalyzes ATP hydrolysis. In this study, we searched a library of small molecule helicase inhibitors for compounds that stimulate ATP hydrolysis catalyzed by the hepatitis C virus (HCV) NS3 heli...

In a previous communication,' it was shown that the helix-coil transition temperature, Tm, of thymus DNA and helical poly A is lowered by pyrimidines, purines, nucleosides, their analogues, and derivatives. The order of their effectiveness indicates that hydrophobic and stacking interactions are important. To investigate the mechanism by which the Tm is reduced is one principal purpose of this ...

A discussion is presented on the mechanism of action of platinum amine compounds, used as antitumor drugs. The relationship between biological acitivity and structure of the compounds is discussed, with special attention to the nature of the ligands coordinated to platinum. The primary biological target appears to be the interaction with nucleic acids, and therefore studies of the interaction o...

Virtual Screening is an increasingly attractive way to discover new small molecules with potential medicinal value. We introduce a novel strategy that integrates use of the molecular docking software Surflex with experimental validation by the method of competition dialysis. This integrated approach was used to identify ligands that selectively bind to the triplex DNA poly(dA)-[poly(dT)](2). A ...

Streptomyces aureofaciens growth in chemically defined medium is actively associated with the secretion of low-molecular-weight nucleic acid-related substances and is linked to low availability of phosphate. Thirteen pure compounds were isolated, of which seven were identified.

Eilatin-containing ruthenium complexes bind to a broad range of different nucleic acids including: calf thymus (CT) DNA, tRNA(Phe), polymeric RNAs and DNAs, and viral RNAs including the HIV-1 RRE and TAR. The nucleic acid specificity of Lambda- and Delta-[Ru(bpy)2eilatin]2+ have been compared to that of the 'free' eilatin ligand, and to the classic intercalating agent ethidium bromide. Interest...

With the realization in 1940 (1) that structural analogues of a metabolite frequently prevent utilization of that metabolite, it became possible to develop antimetabolites which block specific biosynthetic pathways. By blocking various steps in a biosynthetic pathway, antimetabolites are useful for elucidating intermediary metabolism. It was the object of the present study to investigate the bi...