Teaching photosensitizers a new trick: red light-triggered G-quadruplex alkylation by ligand co-localization.

We propose a bimolecular approach for G-quadruplex alkylation, using a pro-reactive furan-containing ligand, activated by red-light irradiation of a proximate G4-binding photosensitizer. G4- over dsDNA alkylation can be achieved selectively and proves high-yielding at low ligand excess. HPLC and modelling studies allowed identifying potential residues involved in the alkylation.

Thermodynamic studies of substrate binding and spin transitions in human cytochrome P-450 3A4 expressed in yeast microsomes.

An approach to the quantitative spectral analysis of substrate binding and inactivation of cytochrome P-450 in microsomes is described. The method is based on the application of the principal component analysis technique on the Soret-region spectra measured at different temperatures at various concentrations of substrate. This approach allowed us to study the thermodynamic parameters of substrate binding and spin transitions in human cytochrome P-450 3A4 expressed in yeast (Saccharomyces cerevisiae) microsomes.

Multiphasic modelling of ligand/acceptor interactions. The hydrophobicity-dependent binding of relatively small amphiphilic substances to acceptor proteins and the nature and facedness of acceptor sites.

The modelling of multiphasic ligand/acceptor equilibrium binding systems proceeds at three logically distinct levels: (1) A suitable response quantity, e.g. the amount of acceptor-bound ligand nEL, is expressed as a function of the ligand concentrations [Li] (L = A,B,.

The substrate-depletion error on the multiple Michaelis-Menten equation with and without an added term linearly dependent on the substrate concentration.

Saturation curves for substrate interaction with an acceptor (enzyme, binding or carrier protein) are often analysed on the assumption that the amount of acceptor-bound substrate is negligible compared to its total amount. Analytical criteria permitting one to decide whether the assumption is justified or not for systems described by a single Michaelis-Menten equation have been derived previously. For more complicated systems, error formulae often cannot be obtained in closed form, and, if obtainable, are unwieldy.

Modelling of interaction of basic lipophilic ligands with cytochrome P-450 reconstituted in liposomes. Determination of membrane partition coefficients of S-(-)-nicotine and N,N-diethylaniline from spectral binding studies and fluorescence quenching.

The spectral interaction of N,N-diethylaniline and S-(-)-nicotine with cytochrome P450IIB4 reconstituted into large unilamellar vesicles could properly be described by a model for interaction of basic lipid-soluble ligands with membrane-bound acceptor sites in which linear partitioning of non-ionized ligand in the membrane is postulated. Apparent spectral dissociation constants Ksapp for type I binding of N,N-diethylaniline and for type II binding of S-(-)-nicotine increased linearly with increasing lipid volume fraction alpha L of the proteoliposomes. From plots of Ksapp vs.