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The oxidation of cytochrome f by the soluble cupredoxin plastocyanin is a central reaction in the photosynthetic electron transfer chain of all oxygenic organisms. Here, two different computational approaches are used to gain new insights into the role of molecular recognition and protein-protein association processes in this redox reaction. First, a(More)
Theoretical descriptors obtained from quantum mechanical calculations on isolated ligands in different media and molecular dynamics simulations of ligand-enzyme complexes have been used to obtain a quantitative rationalization of the inhibition of CYP1A2 and CYP1A2 by three series of flavonoids. Predictive models obtained through one-descriptor QSAR studies(More)
Blue copper proteins are type-I copper-containing redox proteins whose role is to shuttle electrons from an electron donor to an electron acceptor in bacteria and plants. A large amount of experimental data is available on blue copper proteins; however, their functional characterization is hindered by the complexity of redox processes in biological systems.(More)
Novel arylpiperazine derivatives bearing lipophilic probes were designed, synthesized, and evaluated for their potential ability to interact with the 5-hydroxytryptamine(3) (5-HT(3)) receptor. Most of the new compounds show subnanomolar 5-HT(3) receptor affinity. Ester 6bc showing a picomolar K(i) value is one of the most potent 5-HT(3) receptor ligands so(More)
Novel conformationally constrained derivatives of classical 5-HT(3) receptor antagonists were designed and synthesized with the aim of probing the central 5-HT(3) receptor recognition site in a systematic way. The newly-synthesized compounds were tested for their potential ability to inhibit [(3)H]granisetron specific binding to 5-HT(3) receptor in rat(More)
Molecular mechanics methods have been applied to study the interaction between a series of 20 deprotonated benzenesulfonamides and the enzyme carbonic anhydrase. The different contributions to the binding energy have been evaluated and correlated with experimental inhibition data and molecular orbital indices of the sulfonamides in their bound conformation.(More)
A synthetic-computational approach to the study of the binding site of peripheral benzodiazepine receptor (PBR) ligands related to 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxam ide (PK11195, 1) within their receptor has been developed. A wide series of conformationally restrained derivatives of 1 has been designed with the aim of(More)
The synthesis and biological evaluation of a series of 2-substituted 5-phenyl-1,4-benzodiazepines, structurally related to tifluadom (5), the only benzodiazepine that acts simultaneously as a kappa-opioid agonist and a cholecystokinin-A (CCK-A) antagonist, are reported. The radioligand binding models used in these studies were [(125)I](BH)-CCK-8 in rat(More)
The synthesis and biological evaluation of a series of new derivatives of 2-substituted 5-phenyl-1,4-benzodiazepines, structurally related to tifluadom (5), are reported. Chemical and pharmacological studies on compounds 6 have been pursued with the aim of expanding the SAR data and validating the previously proposed model of interaction of this class of(More)
The serotonin 5-HT3 receptor is a ligand-gated ion channel, which by virtue of its pentameric architecture, can be considered to be an intriguing example of intrinsically multivalent biological receptors. This paper describes a general design approach to the study of multivalency in this multimeric ion channel. Bivalent ligands for 5-HT3 receptor have been(More)