Publications associées à Development of Ruthenium Antitumor Drugs that Overcome Multidrug Resistance Mechanisms

From Sequence to Dynamics to Function: Computational Design of Allostery and Ligand Selectivity in G-Protein Coupled Receptors

The phenomenon of allostery, a general property in proteins that has been heralded as "the second secret of life" remains elusive to our understanding and even more challenging to incorporate into protein design. One example of allosteric proteins with gre ...

EPFL2024

Enhancing the Signaling of GPCRs via Orthosteric Ions

Horst Vogel, Shuguang Yuan

G protein-coupled receptors play essential roles in cellular processes such as neuronal signaling, vision, olfaction, tasting, and metabolism. As GPCRs are the most important drug targets, understanding their interactions with ligands is of utmost importan ...

AMER CHEMICAL SOC2020

Crosslinking Allosteric Sites on the Nucleosome Core Particle

Lucinda Kate Batchelor

Designing compounds that bind to the acidic patch of the nucleosome core particle (NCP) is an emerging therapeutic approach that can inhibit the binding of key chromatin factors. Pretreatment of human ovarian carcinoma, A2780, cells with RAPTA-T, an antime ...

EPFL2019

Exploring the role of post-translational modifications in regulating α-synuclein interactions by studying the effects of phosphorylation on nanobody binding

Juan Kiwi, Bruno Claude Daniel Fauvet, Hilal Lashuel, Anass Chiki, Farah El Turk

Intracellular deposits of α-synuclein in the form of Lewy bodies are major hallmarks of Parkinson’s disease (PD) and a range of related neurodegenerative disorders. Post-translational modifications (PTMs) of α-synuclein are increasingly thought to be major ...

2018

Acetylene Oligomerization over Pd Nanoparticles with Controlled Shape: A Parahydrogen-Induced Polarization Study

Lioubov Kiwi, Rocio Micaela Crespo Quesada

Substantial signal enhancements achieved by using parahydrogen in catalytic hydrogenations are powerful tools for mechanistic studies of chemical reactions involving molecular H-2. Potentially, this technique can be extended to other reaction classes, prov ...

American Chemical Society2016

Development of Stapling Methods by Selective Side Chain Modifications of Bioactive Peptides

Christopher Matthew Bandeli Kourra

Cyclic peptide therapeutics fill the gap between small molecules (5000 Da) as a separate class of drugs, combining the advantages of both in terms of high selectivity, bioavailability, synthetic accessibility and low toxicity. Howe ...

EPFL2016

Single-molecule microscopy to study plasma membrane receptor dynamics

Luc Veya

Cell surface receptors allowthe cell to sense and respond to external signals. Receptor malfunctions are associated with many diseases. The diffusional behavior of receptors is of particular interest to understand how the cell modulates receptor function i ...

EPFL2016

Iron Complexes for Hydrogen Activation and Catalytic Hydrogenation

Simona Mazza

Inspired by Nature several groups have developed structural and functional iron complexes mimicking the active site of the iron-hydrogenases, which show high reactivity in the H2 cleavage. Usually pendant bases have been incorporated onto families of Fe co ...

EPFL2015

Identification of Soft Matter Binding Peptide Ligands Using Phage Display

Harm-Anton Klok

Phage display is a powerful tool for the selection of highly affine, short peptide ligands. While originally primarily used for the identification of ligands to proteins, the scope of this technique has significantly expanded over the past two decades. Pha ...

Amer Chemical Soc2015

Ligand substitutions between ruthenium-cymene compounds can control protein versus DNA targeting and anticancer activity

Paul Joseph Dyson, Ursula Röthlisberger, Wee Han Ang, Pablo Campomanes Ramos, Alexey Nazarov, Michael Groessl, Catherine Marie Amélie Clavel

Ruthenium compounds have become promising alternatives to platinum drugs by displaying specific activities against different cancers and favourable toxicity and clearance properties. Nonetheless, their molecular targeting and mechanism of action are poorly ...

Nature Research2014

Naphthalimide-tagged ruthenium-arene anticancer complexes: combining coordination with intercalation

Paul Joseph Dyson, Catherine Marie Amélie Clavel, Fabio Edafe, Kelly Joan Kilpin

Ruthenium(II) arene compounds have been modified with the naphthalimide group, tethered via the arene ligand, i.e. {dichloroeta(6)-N-(phenylalkyl)(4-dimethylamino)-1,8-naphthalimideruthenium(II)} (alkyl = methyl, ethyl, propyl, pta = 1,3,5-triaza-7- ...

American Chemical Society2012

A Fluorescent Sensor for GABA and Synthetic GABA(B) Receptor Ligands

Kai Johnsson, Luc Reymond, Anastasiya Masharina, Keitaro Umezawa

While gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter, suitable tools to measure its concentration in living cells with high spatiotemporal resolution are missing. Herein, we describe the first ratiometric fluorescent sensor for GABA ...

American Chemical Society2012

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

Mitotic Catastrophe Occurs in the Absence of Apoptosis in p53-Null Cells with a Defective G1 Checkpoint

Peter Martin Beard, Michail Fragkos

Cell death occurring during mitosis, or mitotic catastrophe, often takes place in conjunction with apoptosis, but the conditions in which mitotic catastrophe may exhibit features of programmed cell death are still unclear. In the work presented here, we st ...

Public Library of Science2011

Conformational dynamics of cationic cys-loop receptors

Davor Kosanic

Understanding the functional dynamics of ligand-gated ion-channels (LGIC's) on the molecular level is the aim of this thesis. Members of the protein family of LGIC's are involved in the fast synaptic signal transmission and thereby play a central role in i ...

EPFL2009

Novel catalytic applications of carbon nanofibers on sintered metal fibers filters as structured supports

Marina Ruta

Supported metal catalysts are important from both an industrial and a scientific point of view. They are used, amongst others, in large-scale processes such as catalytic reforming, hydrotreating, polymerization reactions and hydrogenations. Often, these ca ...

EPFL2008

Structure-activity relationships for ruthenium(II)-arene drugs : in vitro and in vivo antitumour evaluation

Claudine Scolaro

The discovery of the anticancer properties of cisplatin in 1965 heralded the development of metallopharmaceuticals and founded a revolution in cancer therapy. Platinum drugs are believed to induce cytotoxicity by cross-linking DNA, causing changes to the D ...

EPFL2007

Ampakine CX546 bolsters energetic response of astrocytes: a novel target for cognitive-enhancing drugs acting as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor modulators

Pierre Magistretti, Luc Pellerin

Glutamate was previously shown to enhance aerobic glycolysis i.e. increase glucose utilization and lactate production with no change in oxygen levels, in mouse cortical astrocytes by a mechanism involving glutamate uptake. It is reported here that a simila ...

Wiley-Blackwell2005