Maria Cristina Menziani

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The functional serotonin type-3 receptor (5-HT(3)-R), which is the target of many neuroactive drugs, is known to be a homopentamer made of five identical subunits A (5-HT(3A)-R) or a binary heteropentamer made of subunits A and B (5-HT(3A/B)-R) with a still debated arrangement and stoichiometry. This complex picture has been recently further complicated by(More)
Three-dimensional models of the cytochromes P450 IA2, P450 IID6 and P450 IIIA4 were built by means of comparative modeling using the X-ray crystallographic structures of P450 CAM, P450 BM-3, P450 TERP and P450 ERYF as templates. The three cytochromes were analyzed both in their intrinsic structural features and in their interaction properties with fifty(More)
Interleukin-6 (IL-6) is a pleiotropic cytokine involved in the regulation of proliferation and differentiation of hematopoietic cells and in the pathogenesis of many diseases, including multiple myeloma. This study pursues a way to interfere with IL-6 pathway in an attempt to modulate its biological activity. Here we describe the rational design and(More)
The ability of ad hoc defined size and shape descriptors and theoretical descriptors derived on a single structure to give powerful interpretative and predictive QSAR models has been compared and evaluated with respect to the quality of the pharmacological data available for a series of structurally diverse 5-HT1A receptor antagonists, displaying(More)
This study constitutes a preliminary rationalization, at the molecular level, of antagonist selectivity towards the three cloned alpha 1-adrenergic receptor (alpha 1-AR) subtypes. Molecular dynamics simulations allowed a structural/dynamics analysis of the seven alpha-helix-bundle models of the bovine alpha 1a-, hamster alpha 1b-, and rat alpha 1d-AR(More)
A new computational protocol relying on the use of electrostatic embedding, derived from QM/QM' ONIOM calculations, to simulate the effect of the crystalline environment on the emission spectra of molecular crystals is here applied to the β-form of salicylidene aniline (SA). The first singlet excited states (S1 ) of the SA cis-keto and trans-keto(More)
Multivalency is widely used in nature in specific recognition processes. This paper describes an approach to multivalency in the pentameric 5-HT3 receptor, a ligand-gated ion channel, which constitutes an example of intrinsically multivalent biological receptors. Owing to the picomolar Ki value, TETRA-L represents an outstanding multivalent ligand for the(More)
5-hydroxytryptamine type-3 receptor (5-HT₃), an important target of many neuroactive drugs, is a cation selective transmembrane pentamer whose functional stoichiometries and subunit arrangements are still debated, due to the extreme complexity of the system. The three dimensional structure of the 5-HT₃R subunits has not been solved so far. Moreover, most of(More)
Palonosetron (Aloxi) is a potent second generation 5-HT(3) receptor antagonist whose mechanism of action is not yet fully understood. Palonosetron acts at the 5-HT(3) receptor binding site but recent computational studies indicated other possible sites of action in the extracellular domain. To test this hypothesis we mutated a series of residues in the(More)