Publications related to Ligand efficiency

A scalable CRISPR/Cas9-based fluorescent reporter assay to study DNA double-strand break repair choice

Double-strand breaks (DSBs) are the most toxic type of DNA lesions. Cells repair these lesions using either end protection- or end resection-coupled mechanisms. To study DSB repair choice, we present the Color Assay Tracing-Repair (CAT-R) to simultaneously ...

Nature Research2020

Gas-phase structures reflect the pain-relief potency of enkephalin peptides

Oleg Boyarkine, Vladimir Kopysov, Aleksandr Pereverzev

We use cold ion spectroscopy and quantum-chemical computations to solve the structures of opioid peptides enkephalins in the gas phase. The derived structural parameters clearly correlate with the known pharmacological efficiency of the studied drugs, sugg ...

2019

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

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

A streamlined search technology for identification of synergistic drug combinations

Hubert van den Bergh, Paul Joseph Dyson, Patrycja Nowak-Sliwinska

A major key to improvement of cancer therapy is the combination of drugs. Mixing drugs that already exist on the market may offer an attractive alternative. Here we report on a new model-based streamlined feedback system control (s-FSC) method, based on a ...

Nature Publishing Group2015

Hyperpolarized Water to Study Protein-Ligand Interactions

Geoffrey Bodenhausen, Aurélien Bornet, Sami Jannin, Jonas Milani, Basile Vuichoud, Quentin Chappuis

The affinity between a chosen target protein and small molecules is a key aspect of drug discovery. Screening by popular NMR methods such as Water-LOGSY suffers from low sensitivity and from false positives caused by aggregated or denatured proteins. This ...

2015

Drug Screening Boosted by Hyperpolarized Long-Lived States in NMR

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

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

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

Geoffrey Bodenhausen, Daniele Mammoli, Roberto Buratto

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

Dithiol amino acids can structurally shape and enhance the ligand-binding properties of polypeptides

Christian Heinis, Rudolf Hovius, Florence Pojer, Shiyu Chen, Ranganath Gopalakrishnan

The disulfide bonds that form between two cysteine residues are important in defining and rigidifying the structures of proteins and peptides. In polypeptides containing multiple cysteine residues, disulfide isomerization can lead to multiple products with ...

Nature Publishing Group2014

The Ligand-Based Quintuple Bond-Shortening Concept and Some of Its Limitations

Tobias Bauer

Herein, the ligand-based concept of shortening quintuple bonds and some of its limitations are reported. In dichromium-diguanidinato complexes, the length of the quintuple bond can be influenced by the substituent at the central carbon atom of the used lig ...

Wiley-V C H Verlag Gmbh2013

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

Searching for the Protein Targets of Bioactive Molecules

Kai Johnsson, Christopher Chidley, Cindy Fellay, Hirohito Haruki, Miriam Grønlund Pedersen, Simone Moser

The identification of all protein targets of a given drug or bioactive molecule within the human body is a prerequisite for an understanding of its beneficial and deleterious activities. Current approaches to reveal protein targets often fail to reveal phy ...

Schweizerische Chemische Gesellschaft2011

Structure and function of the nicotinic acetylcholine receptor

Jörg Grandl

The subject of this thesis is the study of the structure and function of the human muscle nicotinic acetylcholine receptor (nAChR), which is a typical member of the large class of ligand-gated ion channels. Appropriate techniques, like site-directed mutage ...

EPFL2005