number of compounds that bind in the minor groove of DNA and exhibit various degree of antitumour activity. Several high resolution crystal and NMR structures have been determined for these ligands bound to short oligonucleotides and provide valuable insights into the details of their interaction. The Hoechst 33258 is bound in the minor groove, with the planar benzimidazole groups oriented para...

In this paper, an analytical formula to calculate the radial stiffness of groove elastic support is presented. The influence of structure parameters on radial stiffness and homogeneity of radial stiffness is investigated as well. The accuracy and calculating speed of the analysis formula are compared to that of finite element method (FEM). Findings are as following: The calculating speed of ana...

An analogue of the DNA-binding compound Hoechst 33258, in which the piperazine ring has been replaced by an imidazoline group, has been cocrystallized with the dodecanucleotide sequence d(CGCGAATTCGCG)2. The structure has been solved by X-ray diffraction analysis and has been refined to an R-factor of 19.7% at a resolution of 2.0 A. The ligand is found to bind in the minor groove, at the centra...

The structure of the 52-amino acid DNA-binding domain of the prokaryotic Hin recombinase, complexed with a DNA recombination half-site, has been solved by x-ray crystallography at 2.3 angstrom resolution. The Hin domain consists of a three-alpha-helix bundle, with the carboxyl-terminal helix inserted into the major groove of DNA, and two flanking extended polypeptide chains that contact bases i...

The best-characterized members of the M23 family are glycyl-glycine hydrolases, such as lysostaphin (Lss) from Staphylococcus simulans or LytM aureus. Recently, enzymes with broad specificities were reported, EnpACD Enterococcus faecalis, that cleaves D,L peptide bond between stem and a cross-bridge. Previously, activity was demonstrated only on isolated peptidoglycan fragments. Herein we repor...

The synthesis and NMR structural studies are reported for a modular threading tetraintercalator bound to DNA. The tetraintercalator design is based on 1,4,5,8-tetracarboxylic naphthalene diimide units connected through flexible peptide linkers. Aided by an overall C(2) symmetry, NMR analysis verified a threading polyintercalation mode of binding, with linkers alternating in the order minor groo...

Mechanical properties of single double-stranded DNA (dsDNA) in the presence of different binding ligands were analyzed in optical-tweezers experiments with subpiconewton force resolution. The binding of ligands to DNA changes the overall mechanic response of the dsDNA molecule. This fundamental property can be used for discrimination and identification of different binding modes and, furthermor...

Recent developments have indicated that aminoglycoside binding is limited not to RNA but to nucleic acids that, like RNA, adopt conformations similar to the A-form. We have further sought to expand the utility of aminoglycoside binding to B-DNA structures by conjugating neomycin, an aminoglycoside antibiotic, with the B-DNA minor groove binding ligand Hoechst 33258. Described herein are novel n...

Binding of human immunodeficiency virus type 1 (HIV-1) transactivator (Tat) protein to Tat-responsive RNA (TAR) is essential for viral replication and is considered a promising starting point for the design of anti-HIV drugs. NMR spectroscopy indicated that the aminoglycosides neomycin B and ribostamycin bind to TAR and that neomycin is able to inhibit Tat binding to TAR. The solution structure...