Determination of the binding epitope of RGD-peptidomimetics to \u3b1v\u3b23 and \u3b1IIb\u3b23 integrin-rich intact cells by NMR and computational studies

NMR experiments (transferred NOE and Saturation Transfer Difference) were used to shed light on the binding epitope of RGD peptidomimetics 1-3 with integrins \u3b1v\u3b23 and \u3b1IIb\u3b23, expressed on the membrane of ECV304 bladder cancer cells and human platelets, respectively. The NMR results were supported by docking calculations in the active sites of \u3b1v\u3b23 and \u3b1IIb\u3b23 integrin receptors and were compared to the results of competitive \u3b1v\u3b23 receptor binding assays and competitive ECV304 cell adhesion experiments. While cis RGD ligand 1 interacts mainly with the \u3b1 integrin subunit through its basic guanidine group, trans RGD ligands 2 and 3 are able to interact with both the \u3b1 and \u3b2 integrin subunits via an electrostatic clam

Exploration of ligand binding modes towards the identification of compounds targeting HuR : a combined STD-NMR and Molecular Modelling approach

Post-transcriptional processes have been recognised as pivotal in the control of gene expression, and impairments in RNA processing are reported in several pathologies (i.e., cancer and neurodegeneration). Focusing on RNA-binding proteins (RBPs), the involvement of Embryonic Lethal Abnormal Vision (ELAV) or Hu proteins and their complexes with target mRNAs in the aetiology of various dysfunctions, has suggested the great potential of compounds able to interfere with the complex stability as an innovative pharmacological strategy for the treatment of numerous diseases. Here, we present a rational follow-up investigation of the interaction between ELAV isoform HuR and structurally-related compounds (i.e., favonoids and coumarins), naturally decorated with diferent functional groups, by means of STD-NMR and Molecular Modelling. Our results represent the foundation for the development of potent and selective ligands able to interfere with ELAV–RNA complexes

Epidemiologic and clinical updates on impulse control disorders: a critical review

The article reviews the current knowledge about the impulse control disorders (ICDs) with specific emphasis on epidemiological and pharmacological advances. In addition to the traditional ICDs present in the DSM-IV—pathological gambling, trichotillomania, kleptomania, pyromania and intermittent explosive disorder—a brief description of the new proposed ICDs—compulsive–impulsive (C–I) Internet usage disorder, C–I sexual behaviors, C–I skin picking and C–I shopping—is provided. Specifically, the article summarizes the phenomenology, epidemiology and comorbidity of the ICDs. Particular attention is paid to the relationship between ICDs and obsessive–compulsive disorder (OCD). Finally, current pharmacological options for treating ICDs are presented and discussed

Diffusion-ordered spectroscopy and saturation transfer difference NMR spectroscopy studies of selective interactions between ELAV protein fragments and an mRNA target

The crucial role of post-transcriptional processes in the control of gene expression opened a new route to translate basic mechanisms into clinical medicine. In this contest, ELAV proteins represent a family of well-characterized proteins that bind mRNA. Interestingly, preliminary data bode well that the ELAV-mediated mRNA stabilization is a mechanism relevant to Alzheimer Disease. Herein we analyzed four peptides, belonging to RNA Recognition Motif of ELAVs, in presence of a mRNA fragment from Tumor Necrosis Factor α, by NMR techniques with the final aim to get insight into the interaction mechanism. Saturation Transfer Difference and Diffusion Order NMR experiments showed that appropriate mixtures of peptides (and not each peptide individually) bind effectively to the biological target. DOSY technique was applied here for the first time to study mRNA:peptides complexes. For each peptide the 3D structure was also determined by NOE analysis supported by molecular dynamics simulation

A Combined NMR-Computational Study of the Interaction between Influenza Virus Hemagglutinin and Sialic Derivatives from Human and Avian Receptors on the Surface of Transfected Cells

The development of small-molecule inhibitors of influenza virus Hemagglutinin could be relevant to the opposition of the diffusion of new pandemic viruses. In this work, we made use of Nuclear Magnetic Resonance (NMR) spectroscopy to study the interaction between two derivatives of sialic acid, Neu5Ac-α-(2,6)-Gal-β-(1–4)-GlcNAc and Neu5Ac-α-(2,3)-Gal-β-(1–4)-GlcNAc, and hemagglutinin directly expressed on the surface of recombinant human cells. We analyzed the interaction of these trisaccharides with 293T cells transfected with the H5 and H1 variants of hemagglutinin, which thus retain their native trimeric conformation in such a realistic environment. By exploiting the magnetization transfer between the protein and the ligand, we obtained evidence of the binding event, and identified the epitope. We analyzed the conformational features of the glycans with an approach combining NMR spectroscopy and data-driven molecular dynamics simulations, thus obtaining useful information for an efficient drug design

Lantibiotic carboxyamide derivatives with enhanced antibacterial activity

Analisi mediante Risonanza Magnetica Nucleare e spettrometria di massa di diverse molecole prodotte da microrganismi o modificate per sintesi. con attivit\ue0 antibiotica. Nel caso di composti particolarmente attivi sono stati condotti studi conformazionali attraverso tecniche di Risonanza Magnetica supportate da analisi computazionale