Dandamudi Usharani

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Subtype selectivity of phosphodiesterase 4 (PDE4) has been proposed to be the most salient feature for the development of drugs for asthma and inflammation. The present review provides an account of various strategies to overcome the side effects of the PDE4 inhibitors. Subtype selectivity and recent developments of molecular modeling approaches towards(More)
The intriguing deactivation of the cytochrome P450 (CYP) 2B4 enzyme induced by mutation of a single residue, Phe429 to His, is explored by quantum mechanical/molecular mechanical calculations of the O-OH bond activation of the (Fe(3+)OOH)(-) intermediate. It is found that the F429H mutant of CYP 2B4 undergoes homolytic instead of heterolytic O-OH bond(More)
DNA-base lesions cause cancer and propagate into the genome. We use in-protein QM/MM calculations to study the repair of etheno-bridged adenine (εA) by the iron(IV)-oxo species of AlkB enzymes. Recent experimental investigations, using mass-spectrometry and in crystallo isolation, suggested that εA was repaired by formation of an epoxide (εA-ep) that(More)
Density functional theory has been applied to elucidate the mechanism of the O-demethylation reaction that generates serotonin from 5-methoxytryptamine (5-MT); a process that is efficiently catalyzed by P450 CYP2D6. Two substrates, the neutral 5-MT and the protonated 5-MTH(+), were used to probe the reactivity of CYP2D6 compound I. Notably, the(More)
We describe herein the hydrogen-atom transfer (HAT)/proton-coupled electron-transfer (PCET) reactivity for Fe(IV)-oxo and Fe(III)-oxo complexes (1-4) that activate C-H, N-H, and O-H bonds in 9,10-dihydroanthracene (S1), dimethylformamide (S2), 1,2-diphenylhydrazine (S3), p-methoxyphenol (S4), and 1,4-cyclohexadiene (S5). In 1-3, the iron is pentacoordinated(More)
The intramolecular gas-phase reactivity of four oxoiron(IV) complexes supported by tetradentate N(4) ligands (L) has been studied by means of tandem mass spectrometry measurements in which the gas-phase ions [Fe(IV)(O)(L)(OTf)](+) (OTf = trifluoromethanesulfonate) and [Fe(IV) (O)(L)](2+) were isolated and then allowed to fragment by collision-induced decay(More)
This theoretical work addresses the mechanistic switch between hydroxylase (alcohol formation) and desaturase (olefin formation) activities during alkane oxidation by two non-heme high-valent oxoiron reagents, the enzyme taurine:α-ketoglutarase dioxygenase (TauD) and the synthetic shape-selective catalyst (TpOBzFe), toward cyclohexadiene, cyclohexane,(More)
Here, we present the synthesis, photochemical, and DNA binding properties of three photoisomerizable azobenzene-distamycin conjugates in which two distamycin units were linked via electron-rich alkoxy or electron-withdrawing carboxamido moieties with the azobenzene core. Like parent distamycin A, these molecules also demonstrated AT-specific DNA binding.(More)
The structural basis of the regulation of microsomal cytochrome P450 (P450) activity was investigated by mutating the highly conserved heme binding motif residue, Phe429, on the proximal side of cytochrome P450 2B4 to a histidine. Spectroscopic, pre-steady-state and steady-state kinetic, thermodynamic, theoretical, and structural studies of the mutant(More)