Publications associées à Yeast Three-Hybrid Screening for Identifying Anti-Tuberculosis Drug Targets

Generating macrocyclic inhibitors of protein-protein interactions

Protein-protein interactions (PPIs) play important roles in many diseases and their modulation is an attractive strategy for developing new therapeutics. However, the relatively large and often flat binding surfaces of PPIs makes the development of inhibit ...

EPFL2022

Synthesis and direct assay of large macrocycle diversities by combinatorial late-stage modification at picomole scale

Gerardo Turcatti, Jonathan Patrice Vesin, Christian Heinis, Alessandro Angelini, Gontran Sangouard, Julien Bortoli Chapalay, Mischa Schüttel, Ganesh Kumar Mothukuri, Manuel Leonardo Merz, Sevan Mleh Habeshian, Cristina Diaz Perlas, Zsolt Bognár

Macrocycles have excellent potential as therapeutics due to their ability to bind challenging targets. However, generating macrocycles against new targets is hindered by a lack of large macrocycle libraries for high-throughput screening. To overcome this, ...

Nature Research2022

De novo developed small cyclic peptides that are orally available

Manuel Leonardo Merz

Cyclic peptides are ring-shaped molecules that emerged as a promising class of therapeutics. While it is often difficult to find small molecule binders for challenging disease targets, cyclic peptides can bind to featureless surfaces or inhibit protein-pro ...

EPFL2022

Methods for the generation of large combinatorial macrocycle libraries

Sevan Mleh Habeshian

Macrocycles are an attractive class of molecules due to their good binding properties and yet rather small size that allows, in many cases, crossing membranes to reach intracellular targets. In comparison to classical small molecule drugs, macrocycles are ...

EPFL2021

Establishing a Ternary System for Optical Monitoring of DNA-Protein Interactions with Single-Walled Carbon Nanotubes

Shang-Jung Wu

DNA-protein interactions lie at the crux of life's essential processes. As such, various technologies have been developed to characterize these interactions. The distinct advantages of these technologies can be leveraged to study different facets of these ...

EPFL2020

Generation of a Large Peptide Phage Display Library by Self-Ligation of Whole-Plasmid PCR Product

Christian Heinis, Xudong Kong, Kaycie Marie Butler, Vanessa Carle, Cristina Diaz Perlas

The success of phage display, used for developing target-specific binders based on peptides and proteins, depends on the size and diversity of the library screened, but generating large libraries of phage-encoded polypeptides remains challenging. New pepti ...

2020

The functional proteome landscape of Escherichia coli

Camille Véronique Bernadette Goemans

Recent developments in high-throughput reverse genetics1,2 have revolutionized our ability to map gene function and interactions3,4,5,6. The power of these approaches depends on their ability to identify functionally associated genes, which elicit similar ...

2020

High-throughput microfluidic platforms for characterizing and engineering cell-free gene regulatory circuits

Zoe Newell Swank

Cell-free systems have emerged as a versatile platform for constructing complex biological systems from the bottom-up. In particular, they enable the rapid engineering and characterization of gene regulatory networks, a critical cellular subsystem that all ...

EPFL2020

Integrated microfluidic tools for the characterization of protein/DNA interactions in vitro and in vivo

Riccardo Dainese

The specific interaction between DNA and proteins constitutes one of the crucial elements in the regulation of gene expression. This thesis focuses on the development and optimization of two microfluidic-based technologies called SMiLE-seq and FloChIP that ...

EPFL2019

Design and validation of bioorthogonal probes for cellular disease models

Pier Luca D'Alessandro

Well-validated chemical probes enable testing of biological hypotheses, investigation of target tractability and translatability to the clinical phase. Consequently, these important tool compounds play a key role in the drug discovery process. Moreover, th ...

EPFL2019

Innovative Tools and in vivo Methods for Tuberculosis Drug Discovery and Development

Raphael Christopher Sommer

Worldwide, tuberculosis (TB) is the leading cause of death due to a single infectious agent, claiming 1.6 million human lives and causing >10 million new cases in 2017 alone, mostly in low-income regions. The intracellular pathogen Mycobacterium tuberculos ...

EPFL2019

An optimized and validated 384-well plate assay to test platelet function in a high-throughput screening format

Nikolaos Stergiopoulos, Marc Chambon, Olivier Burri, Rodrigo Araujo Fraga Da Silva, Fabiana Pereira Da Costa Fraga, Julien Bortoli Chapalay, Maiia Bragina, Augusto Martins Lima

Despite significant advances in the treatment of cardiovascular diseases, antiplatelet therapies are still associated with a high risk of hemorrhage. In order to develop new drugs, methods to measure platelet function must be adapted for the high-throughpu ...

TAYLOR & FRANCIS INC2019

Monitoring Tuberculosis Drug Activity in Live Animals by Using Near-Infrared Fluorescence Imaging

Stewart Cole, Raphael Christopher Sommer

Worldwide, tuberculosis (TB) is the leading cause of death due to infection with a single pathogenic agent, Mycobacterium tuberculosis. In the absence of an effective vaccine, new, more powerful antibiotics are required to halt the growing spread of multid ...

AMER SOC MICROBIOLOGY2019

A novel cell-based sensor detecting the activity of individual basic proprotein convertases

Daniel Constam, Karin Irmgard Löw, Stefan Kunz

The basic proprotein convertases (PCs) furin, PC1/3, PC2, PC5/6, PACE4, PC4, and PC7 are promising drug targets for human diseases. However, developing selective inhibitors remains challenging due to overlapping substrate recognition motifs and limited str ...

WILEY2019

Analytical Approaches for Monitoring DNA–Protein Interactions

Ardemis Anoush Boghossian, Shang-Jung Wu

DNA–protein interactions play a critical role in cellular regulation. We herein review existing analytical methods for investigating these interactions, highlighting methods such as chromatin immunoprecipitation and yeast-one-hybrid that are used to identi ...

2019

Development and validation of a multiplex UHPLC-MS/MS method for the determination of the investigational antibiotic against multi-resistant tuberculosis macozinone (PBTZ169) and five active metabolites in human plasma

Thierry Buclin, Stewart Cole, Jeff Pitteloud, Anthony Vocat

The emergence of Mycobacterium tuberculosis strains resistant to current first-line antibiotic regimens constitutes a major global health threat. New treatments against multidrug-resistant tuberculosis (MDR-TB) are thus eagerly needed in particular in coun ...

2019

More Medicines for Tuberculosis: Fuelling Drug Discovery against Mycobacterium tuberculosis

Shi-Yan Caroline Foo

Tuberculosis (TB), whose etiological agent is Mycobacterium tuberculosis (M. tuberculosis), has plagued humanity since antiquity. Even with chemotherapy available today, TB is the leading cause of death due to an infectious disease. Modern day factors, suc ...

EPFL2018

Arylvinylpiperazine Amides, a New Class of Potent Inhibitors Targeting QcrB of Mycobacterium tuberculosis

Stewart Cole, Raphael Christopher Sommer, Shi-Yan Caroline Foo, Anthony Vocat, Andrej Benjak, Jérémie Piton, Andréanne Lupien

New drugs are needed to control the current tuberculosis (TB) pandemic caused by infection with Mycobacterium tuberculosis. We report here on our work with AX-35, an arylvinylpiperazine amide, and four related analogs, which are potent antitubercular agent ...

AMER SOC MICROBIOLOGY2018

Development of microfluidic tools and methods for the biochemical characterization of scFv and Cas9 affinity reagents and their applications in molecular detection

Ekaterina Emilova Petrova

Recent progress in protein engineering, empowered by the rapidly evolving fields of synthetic biology and DNA synthesis, has enabled the generation of various custom-designed proteins. Their thorough analysis has led to applications in areas including medi ...

EPFL2018

Microfluidic platforms for high-throughput mammalian cell printing, transfection, and dosage-dependent studies

Kristina Pan Woodruff

With the advent of high-throughput and genome-wide screening initiatives, there is a need for improved methods for cell-based assays. Current approaches require expensive equipment, rely on large-scale culturing formats not suited for small or rare sample ...

EPFL2017