Intercalating, minor groove binding, and covalently bonding drugs were evaluated by mobility shift assays for their ability to interfere with transcription factors binding to their respective DNA recognition sequences. The Cys2His2 zinc finger proteins EGR1, WT1, and NIL2A, the basic leucine-zipper protein wbJun/wbFos, and the minor groove binding protein hTBP were chosen as representative tran...

The objective of this thesis was to study whether heterocyclic dicationic compounds that are minor groove binders have the ability to inhibit the digestive properties of type II restriction enzymes which bind to the major groove of the DNA. If these compounds do possess the ability to inhibit restriction enzymes, then what factors influence their ability to inhibit the restriction enzymes? The ...

Explicit solvent and counterion molecular dynamics simulations have been carried out for a total of >80 ns on the bacterial and spinach chloroplast 5S rRNA Loop E motifs. The Loop E sequences form unique duplex architectures composed of seven consecutive non-Watson-Crick basepairs. The starting structure of spinach chloroplast Loop E was modeled using isostericity principles, and the simulation...

Fluorescence titration measurements have been used to examine the binding interaction of a number of analogues of the bis -benzimidazole DNA minor groove binding agent Hoechst 33258 with the decamer duplex d(GCAAATTTGC)2. The method of continuous variation in ligand concentration (Job plot analysis) reveals a 1:1 binding stoichiometry for all four analogues; binding constants are independent of...

Two-dimensional homonuclear NMR was used to characterize synthetic DNA minor groove-binding ligands in complexes with oligonucleotides containing three different A-T binding sites. The three ligands studied have a C(2) axis of symmetry and have the same general structural motif of a central para-substituted benzene ring flanked by two meta-substituted rings, giving the molecules a crescent shap...

Recognition of signal sequences by cognate receptors controls the entry of virtually all proteins to export pathways. Despite its importance, this process remains poorly understood. Here, we present the solution structure of a signal peptide bound to SecA, the 204 kDa ATPase motor of the Sec translocase. Upon encounter, the signal peptide forms an alpha-helix that inserts into a flexible and el...

Small minor groove binding molecules have been found to influence DNA-dependent processes. Their affinity is high enough to prevent transcription factors from interaction with the DNA. Some of the minor groove binders can be even designed to target only specific DNA sequences. Thereby, they are able to influence transcription, which provides the possibility to systematically regulate the synthe...

Heat shock genes are activated by the binding of the heat shock transcription factor (HSF) to heat shock elements (HSEs), consisting of arrays of the 5-bp unit NGAAN arranged as inverted repeats. Here, we have investigated the interaction of the 5-bp unit with HSFs of Drosophila and Saccharomyces. Mutations within the conserved, central trinucleotide GAA reduce the relative binding affinity of ...