Publications associées à Reactivity of an antimetastatic organometallic ruthenium compound with metallothionein-2: relevance to the mechanism of action

Structural Basis of the Allosteric Inhibition of Human ABCG2 by Nanobodies

Henning Paul-Julius Stahlberg, Dongchun Ni

ABCG2 is an ATP-binding cassette transporter that exports a wide range of xenobiotic compounds and has been recognized as a contributing factor for multidrug resistance in cancer cells. Substrate and inhibitor interactions with ABCG2 have been extensively ...

Academic Press Ltd- Elsevier Science Ltd2023

Systematic analysis of biomolecular binding reactions using microfluidic systems

Amir Shahein

Transcription factor binding to a single binding site on DNA and its functional consequence in a promoter context are beginning to be relatively well understood. However, binding to clusters of sites has yet to be characterized in depth, and the functional ...

EPFL2022

Pharmacological characterization of mutant huntingtin aggregate-directed PET imaging tracer candidates

Hilal Lashuel, Anass Chiki

Huntington's disease (HD) is caused by a CAG trinucleotide repeat expansion in the first exon of the huntingtin (HTT) gene coding for the huntingtin (HTT) protein. The misfolding and consequential aggregation of CAG-expanded mutant HTT (mHTT) underpin HD p ...

Nature Portfolio2021

Structural Basis of Ligand Selectivity by a Bacterial Adhesin Lectin Involved in Multispecies Biofilm Formation

Corey Alfred Stevens

Carbohydrate recognition by lectins governs critical host-microbe interactions. MpPA14 (Marinomonas primoryensis PA14 domain) lectin is a domain of a 1.5-MDa adhesin responsible for a symbiotic bacterium-diatom interaction in Antarctica. Here, we show that ...

Amer Soc Microbiology2021

Targeting the oncogenic signaling of the transcription factor STAT3 with potent and selective monobody inhibitors

Grégory La Sala

Many targeted cancer therapies fail to improve the overall survival of patients. Limitations involve low drug selectivity and the rapid development of resistance. Moreover, the majority of oncogenic drivers presently remain considered as undruggable as th ...

EPFL2020

Mechanics of Allostery: Contrasting the Induced Fit and Population Shift Scenarios

Solange Marie Flatt, Matthieu Wyart, Stefano Zamuner, Riccardo Ravasio, Carolina Brito Carvalho dos Santos

In allosteric proteins, binding a ligand can affect function at a distant location, for example, by changing the binding affinity of a substrate at the active site. The induced fit and population shift models, which differ by the assumed number of stable c ...

CELL PRESS2019

Allosteric Protein Switches based on Antibody Mimetics

Helen Rebecca Ostlund Farrants

Synthetic protein switches are proteins that can be controlled by an external input, and are useful tools to probe protein function. Antibody fragments and antibody mimetics can be selected to bind, activate, or inhibit several diverse protein targets. Nev ...

EPFL2019

Non-covalent albumin-binding ligands for extending the circulating half-life of small biotherapeutics

Alessandro Angelini, Alessandro Zorzi, Sara Linciano

Peptides and small protein scaffolds are gaining increasing interest as therapeutics. Similarly to full-length antibodies, they can bind a target with a high binding affinity and specificity while remaining small enough to diffuse into tissues. However, de ...

ROYAL SOC CHEMISTRY2019

A novel psychoanalytical approach: An electrochemical ligand-binding assay to screen antipsychotics

Sandro Carrara, Tugba Kilic

Schizophrenia treatment may see a paradigm shift due to development of new atypical antipsychotic drugs (APDs), with better tolerability due to more selective dopamine (DA) receptor blockade. Monitoring of these APD candidates in biological fluids is of gr ...

2018

Real-time binding kinetics of ligand-receptor interactions : development and application of a label-free optical biosensor for living bacteria

Ekaterina Rostova

In principle, a major goal in drug development is to design a high-affinity compound with an appropriate pharmacological response, which requires understanding of physical processes underlying the drug-target interaction, affinity and specificity. This dru ...

EPFL2017

Homogeneous time-resolved G protein-coupled receptor-ligand binding assay based on fluorescence cross-correlation spectroscopy

Luc Henry

G protein-coupled receptors (GPCRs) mediate many important physiological functions and are considered as one of the most successful therapeutic target classes for a wide spectrum of diseases. Drug discovery projects generally benefit from a broad range of ...

Academic Press Inc Elsevier Science2016

On the role of water density fluctuations in the inhibition of a proton channel

Lucie Monique Françoise Delemotte

Hv1 is a transmembrane four-helix bundle that transports protons in a voltage-controlled manner. Its crucial role in many pathological conditions, including cancer and ischemic brain damage, makes Hv1 a promising drug target. Starting from the recently sol ...

National Academy of Sciences2016

Screening of structurally diverse bicyclic peptide libraries by phage display

Davide Bertoldo

Bicyclic peptides are an attractive molecule format for the development of therapeutics and research tools. Our laboratory is specialized on the development of bicyclic peptide ligands by phage display. In brief, libraries of randompeptides each containing ...

EPFL2016

Exploring Weak Ligand-Protein Interactions by Long-Lived NMR States: Improved Contrast in Fragment-Based Drug Screening

Geoffrey Bodenhausen, Roberto Buratto, Daniele Mammoli

Ligands that have an affinity for protein targets can be screened very effectively by exploiting favorable properties of long-lived states (LLS) in NMR spectroscopy. In this work, we describe the use of LLS for competitive binding experiments to measure ac ...

Wiley-Blackwell2014

Drug Screening Boosted by Hyperpolarized Long-Lived States in NMR

Geoffrey Bodenhausen, Sandrine Gerber, Sami Jannin, Aurélien Bornet, Jonas Milani, Basile Vuichoud, Nicola Salvi, Solène Marcelle Françoise Marie Passemard, Roberto Buratto, Aurélien Laguerre, Daniele Mammoli, Maninder Singh

Transverse and longitudinal relaxation times (T11 and T1) have been widely exploited in NMR to probe the binding of ligands and putative drugs to target proteins. We have shown recently that long-lived states (LLS) can be more sensitive to ligand binding. ...

Wiley-Blackwell2014

Increasing the Efficiency of Ligands for FK506-Binding Protein 51 by Conformational Control

Ranganath Gopalakrishnan

The design of efficient ligands remains a key challenge in drug discovery. In the quest for lead-like ligands for the FK506-binding protein 51 (FKBP51), we designed two new classes of bicyclic sulfonamides to probe the contribution of conformational energy ...

Amer Chemical Soc2013

A Biochemical and Biophysical Investigation of 5-HT3 Receptor Stability

Menno Berend Tol

The 5-hydroxytryptamine 3 receptor (5-HT3R) is a member of the pentameric ligand-gated ion channel (pLGIC) family, that plays an important role in fast signal transduction and cell-cell communication in synapses: They convert a chemical signal from a neuro ...

EPFL2012

Probing Odorant-Mediated Receptor Activation

Olivia Baud

Molecular interactions of odorants with their olfactory receptors (ORs) are of central importance for the mammalian olfactory system to detect and discriminate a large variety of odors with a limited set of receptors. How a particular OR binds and distingu ...

EPFL2012

Rationalization of the inhibition activity of structurally related organometallic compounds against the drug target cathepsin B by DFT

Paul Joseph Dyson, Angela Casini, Fabio Edafe

A series of organometallic compds. of general formula [(arene)M(PTA)nXm]Y (arene = η6-C10H14, η-C5Me5); (M = Ru(II), Os(II), Rh(III) and Ir(III); X = Cl, mPTA; Y = OTf, PF6) have been screened for their cytotoxicity and ability to inhibit cathepsin B in vi ...

Royal Society of Chemistry2010

Characterization of the 5HT3 receptor in live cells and in vitro : heterologous expression, isolation and reconstitution in lipid membranes

Veronica Ponce de Leon

The serotonin type 3 receptor (5HT3R) is a homopentameric, cation selective channel that mediates fast excitatory transmission in the nervous system. It is a member of the Cys-loop family of receptors that include the nicotinic acetylcholine receptor (nACh ...

EPFL2009