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FtsZ, an essential cytokinesis protein, was a highly promising target for antibacterial agents. Following up the identification of trisubstituted benzimidazoles targeting Mycobacterium tuberculosis FtsZ ( Mtb FtsZ) in previous studies and in order to explore the possible binding mode of these analogues, in silico methodologies such as 3D-QSAR, ProFunc analysis, molecular docking and molecular dynamic simulation were performed. They corroborated well with each other and gave credence to the proposed binding mechanism of trisubstituted benzimidazoles in the interdomain cleft region of Mtb FtsZ. The benzimidazole scaffold and cyclohexyl group of trisubstituted benzimidazoles were orthogonal to each other in low energy state and inclosed in a most hydrophobic environment formed by residues from the C-terminal β sheets and H7 helix. The carbamate groups at the 5-position extended outward form the cleft cavity to the hydrophilic surface. The substituents at the 6-position fitted into the top portion of the cleft by directly interacting with the T7 loop. It was believed that the hydrophobic interactions and the polar contacts were major contributors to the stabilization of the ligand binding in the interdomain cleft. The binding mechanism provided useful clues to design new trisubstituted benzimidazoles inhibitors of Mtb FisZ with promising activity. The work presented here may even be expanded tremendously to screen novel Mtb FtsZ inhibitors with different scaffolds by using the molecular dynamic refined Mtb FtsZ structure and docking based 3D QSAR CoMFA. Graphical Abstract: [ABSTRACT FROM AUTHOR]

Circular dichroism (CD) spectra of complexes of 4-benzylaminopyrimido[4′,5′ :4,5]selenolo(2,3-b)quinoline (BAPSQ) with octanucleotide I (d(TGACGTCA)), which is the cAMPresponsive element (CRE) in gene promoters, and its inverse d(ACTGCAGT) (octanucleotide II) have been measured over a range of drug/DNA ratios. It was demonstrated that the anticancer polyaromatic drug BAPSQ intercalates into DNA basepairs with its long direction perpendicular to both the DNA helix axis and the base pair long axis and induces larger conformational changes in CpG containing octanucleotide I CRE than in its reverse sequence, octanucleotide II. It was concluded that CD is a powerful and sensitive technique to discriminate between drug-binding modes of DNA and to define the geometry of the chromophore inserted into base pairs. [ABSTRACT FROM AUTHOR]

Complexes of DNA with actinocin derivatives containing benzocrown groups at positions 1 and/or 9 of the chromophore were studied by spectrophotometric titration and circular dichroism. The actinocin chromophore and the crown fragments are the DNA-binding sites of the ligands. The mode of ligand–DNA binding is shown to depend on the size of the crown group, its distance to the actinocin chromophore, and the ionic strength of the medium. Na+-selective benzocrown fragments combine with DNA phosphate groups. The simultaneous interaction of the actinocin chromophore with the DNA bases is possible only at an optimal distance between the two binding sites of ligand molecule. [ABSTRACT FROM AUTHOR]

The inhibition in the rate of hydrolysis of four esters, by the anionic micelles of sodium laurylsulphate has been explained by a binding model. It provides the critical micelle concentration under reaction conditions. Kinetic data suggest that more than 90% of the substrate is micelle-bound at 0.010 M concentration of the anionic micelle and the binding constants obtained agree with those of other systems studied elsewhere. The marked inhibition in the comicellar phase and the cationic micellar phase of sodium Iaurylsulphate, cetyldimethylbenzylammonium chloride or cetyltrimethylammonium bromide, has been explained by using the same pseudo model and the binding constant, K and the fraction of substrate held at the comicellar surface, F , indicates greater binding at the comicellar surface. The cooperativity treatment has been extended to micelle-inhibited reactions and the proposed model has been tested with literature data as well as in the present work. The cooperativity index value ranges from 0.59 to 1.51, and a value less than unity indicates negative cooperativity. [ABSTRACT FROM AUTHOR]

We recently presented evidence showing that the visible CD spectrum of the purple membrane from Halobacterium halobium consists of two contributions: a broad positive band centered at the absorption maximum due to the interaction of the chromophore with the protein to which it is bound, and an exciton coupling band due to the interaction between chromophores of adjacent bacteriorhodopsin molecules in the hexagonal surface lattice (Heyn et al., 1975). This interpretation receives strong support from the present experiments in which the chromophore-free membrane is reconstituted by the addition of retinal. Since the coupling signal arises from the interaction between pairs of neighboring chromophores, its contribution to the spectrum would be expected to be very small in the initial stages of the titration experiment, but increasing quadratically with the percentage reconstitution. The broad positive band, on the other hand, is expected to increase linearly with the percentage reconstitution. On the basis of these considerations a satisfactory explanation of the CD reconstitution experiments could be given. Since it appears to be impossible to explain the titration experiments without the quadratic term, we conclude that chromophore-chromophore interactions play an important role. No significant changes in secondary structure upon reconstitution could be detected consistent with our binding model which neglects cooperativity. [ABSTRACT FROM AUTHOR]