Publications related to Method and compositions for inhibition of macrophage migration inhibitory factor (mif)

Development of cysteine cathepsin inhibitors combined with cell type-specific delivery for the treatment of B-cell lymphoma and solid tumors

Cysteine cathepsins proteases are enzymes that play essential physiological roles, but their activity is also associated to different aspects of cancer progression and to the development of other diseases. Therefore, cysteine cathepsins are relevant and pr ...

EPFL2024

De novo designed proteins: a study in engineering novel folds and functions

Alexandra Krina Van Hall-Beauvais

Proteins control nearly every facet of life on a molecular level. Proteins are formed from linear strings of amino acids, which fold into three-dimensional structures that can enact functions. Evolution has created highly efficient proteins in diverse fold ...

EPFL2023

Polyanionic Amphiphilic Dendritic Polyglycerols as Broad-Spectrum Viral Inhibitors with a Virucidal Mechanism

Francesco Stellacci, Valeria Cagno, Matteo Gasbarri

Heparin has been known to be a broad-spectrum inhibitor of viral infection for almost 70 years, and it has been used as a medication for almost 90 years due to its anticoagulant effect. This nontoxic biocompatible polymer efficiently binds to many types of ...

American Chemical Society2022

Investigation of Carboxylic Acid Isosteres and Prodrugs for Inhibition of the Human SIRT5 Lysine Deacylase Enzyme

Alexander Lund Nielsen

Sirtuin 5 (SIRT5) is a protein lysine deacylase enzyme that regulates diverse biology by hydrolyzing epsilon-N-carboxyacyllysine posttranslational modifications in the cell. Inhibition of SIRT5 has been linked to potential treatment of several cancers but ...

Wiley-VCH Verlag GmbH2022

Two-step immobilization of metronidazole prodrug on TEMPO cellulose nanofibrils through thiol-yne click chemistry for in situ controlled release

David Lyndon Emsley, Jasmine Viger-Gravel, Michel Bardet, Julien Bras

Nowadays, drug encapsulation and drug release from cellulose nanofibrils systems are intense research topics, and commercial grades of cellulose nanomaterials are currently available. In this work we present an ester-containing prodrug of metronidazole tha ...

ELSEVIER SCI LTD2021

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

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

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

Identification and characterisation of small-molecule inhibitors targeting STING

Simone Margret Haag

The recognition of pathogen-derived nucleic acids is a critical mechanism by which the innate immune system detects viral infection. Upon activation, nucleic acid sensors initiate the expression of type I interferons and other inflammatory mediators, subse ...

EPFL2019

Site-Specific Polymer Attachment to HR2 Peptide Fusion Inhibitors against HIV-1 Decreases Binding Association Rates and Dissociation Rates Rather Than Binding Affinity

Harm-Anton Klok, Maarten Danial, Frederik Roman Wurm

A popular strategy for overcoming the limited plasma half-life of peptide heptad repeat 2 (HR2) fusion inhibitors against HIV-1 is conjugation with biocompatible polymers such as poly(ethylene glycol) (PEG). However, despite improved resistance to proteoly ...

2017

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

Characterization of DprE1-Mediated Benzothiazinone Resistance in Mycobacterium tuberculosis

Gaëlle Séraphine Kolly, Stewart Cole, Claudia Sala, Benoit Lechartier, Joao Pedro De Almeida Neres, Stefanie Boy-Röttger, Jan Lars Rybniker, Shi-Yan Caroline Foo, Jérémie Piton, Andréanne Lupien

Benzothiazinones (BTZs) are a class of compounds found to be extremely potent against both drug-susceptible and drug-resistant Mycobacterium tuberculosis strains. The potency of BTZs is explained by their specificity for their target decaprenylphosphoryl-D ...

American Society for Microbiology2016

Alkaline phosphatase-fused repebody as a new format of immuno-reagent for an immunoassay

Oliver Hantschel

Enzyme-linked immunoassays based on an antibody-antigen interaction are widely used in biological and medical sciences. However, the conjugation of an enzyme to antibodies needs an additional chemical process, usually resulting in randomly cross-linked mol ...

Elsevier2016

Real-Time Label-Free Direct Electronic Monitoring of Topoisomerase Enzyme Binding Kinetics on Graphene

Klaus Kern, Kannan Balasubramanian

Mono layer graphene field-effect sensors operating in liquid have been widely deployed for detecting a range of analyte species often under equilibrium conditions. Here we report on the real-time detection of the binding kinetics of the essential human enz ...

Amer Chemical Soc2015

Structural insights on cholesterol endosynthesis: Binding of squalene and 2,3-oxidosqualene to supernatant protein factor

Michele Cascella, Maria Josefina Marcaida Lopez, Christos Lamprakis

We present the crystal structures of the SEC14-like domain of supernatant protein factor (SPF) in complex with squalene and 2,3-oxidosqualene. The structures were resolved at 1.75 angstrom (complex with squalene) and 1.6 angstrom resolution (complex with 2 ...

Elsevier2015

Reversible supramolecular modification of surfaces

Negar Moridi

Enzymes are biocatalysts widely used in a large number of industrial biotech processes as they offer clear advantages over their chemical counterparts. Indeed, enzymes often show high substrate selectivity along with elevated turnover rates. Enzymatic cata ...

EPFL2015

How Structural and Physicochemical Determinants Shape Sequence Constraints in a Functional Enzyme

Matteo Dal Peraro, Luciano Andres Abriata

The need for interfacing structural biology and biophysics to molecular evolution is being increasingly recognized. One part of the big problem is to understand how physics and chemistry shape the sequence space available to functional proteins, while sati ...

Public Library Science2015

Phage Selection of Bicyclic Peptides and High-Throughput Screening of Chemical Compounds for the Identification of Novel Inhibitors of the Notch Pathway

Charlotte Marie Urech-Varenne

Notch signaling is a highly conserved developmental pathway that plays important roles in the regulation of cellular processes including cell fate decisions and stem cell maintenance. A tight regulation of the Notch cascade ensures proper tissue homeostasi ...

EPFL2015

Towards a new combination therapy for tuberculosis with next generation benzothiazinones

Paul Joseph Dyson, Thierry Buclin, Stewart Cole, Florence Pojer, Ruben Hartkoorn, Ming Zhang, Benoit Lechartier, Joao Pedro De Almeida Neres, Anthony Vocat

The benzothiazinone lead compound, BTZ043, kills Mycobacterium tuberculosis by inhibiting the essential flavo-enzyme DprE1, decaprenylphosphoryl-beta-D-ribose 2-epimerase. Here, we synthesized a new series of piperazine-containing benzothiazinones (PBTZ) a ...

2014

Reaction Mechanism and Catalytic Fingerprint of Allantoin Racemase

Matteo Thomas Degiacomi, Thomas Lemmin, Matteo Dal Peraro, Marco Stenta, Christophe Bovigny

The stereospecific oxidative decomposition of urate into allantoin is the core of purine catabolism in many organisms. The spontaneous decomposition of upstream intermediates and the nonenzymatic racemization of allantoin lead to an accumulation of (R)-all ...

Amer Chemical Soc2014