Publications associées à DprE1 as a Drug Target from Mycobacterium Tuberculosis

Antibody-peptide conjugates for targeted inhibition of cysteine proteases

We developed a rational approach to design peptide-based covalent inhibitors and coupled the inhibitors with antibodies for cell-specific delivery. We used this platform to generate antibody-peptide inhibitor conjugates (APICs) that target a family of prot ...

Nature Portfolio2024

Single-cell analysis of the interactions between Mycobacterium tuberculosis and macrophages

Ophélie Rutschmann

Mycobacterium Tuberculosis is a highly effective pathogen infecting nearly a third of the world's population. An M. tuberculosis infection starts when droplets containing bacteria enter an individual's lungs. The first host cells to contact the bacteria ar ...

EPFL2024

Bacterial diversity dominates variable macrophage responses of tuberculosis patients in Tanzania

Jacques Fellay, Zhi Ming Xu

The Mycobacterium tuberculosis complex (MTBC) comprises nine human-adapted lineages that differ in their geographical distribution. Local adaptation of specific MTBC genotypes to the respective human host population has been invoked in this context. We aim ...

Nature Portfolio2024

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

Aaron Simone Petruzzella

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

Optimality principles for the analysis of biological processes across scales: From enzyme kinetics to microbiome dynamics

Asli Sahin

Microorganisms are essential for life on Earth, performing key roles in numerous biological processes. Their influence extends across a wide spectrum, from human health and ecological balance to advancements in biotechnology and industrial applications. Th ...

EPFL2024

The simultaneous Selective Catalytic Reduction of N2O and NO over Fe-exchanged zeolites

Filippo Buttignol

Iron-exchanged zeolites are industrial heterogeneous catalysts deployed to remediate anthropogenic emissions of both nitrous oxide (N2O) and nitrogen oxides (NOx = NO + NO2). Despite the extensive scientific attention received, limited knowledge is availab ...

EPFL2024

Human alveolar lining fl uid from the elderly promotes Mycobacterium tuberculosis intracellular growth and translocation into the cytosol of alveolar epithelial cells

Vivek Vijay Thacker, Richa Mishra

The elderly population is highly susceptible to developing respiratory diseases, including tuberculosis, a devastating disease caused by the airborne pathogen Mycobacterium tuberculosis ( M.tb ) that kills one person every 18 seconds. Once M.tb reaches the ...

Elsevier Science Inc2024

Optimal enzyme utilization suggests that concentrations and thermodynamics determine binding mechanisms and enzyme saturations

Vassily Hatzimanikatis, Daniel Robert Weilandt, Asli Sahin

One of the main challenges hampering the development of kinetic models is the lack of kinetic parameters for many enzymatic reactions. Here, the authors introduce a framework to explore the catalytically optimal operating conditions of any complex enzyme m ...

Nature Portfolio2023

Investigating the composition and recruitment of the mycobacterial ImuA'-ImuB-DnaE2 mutasome

John McKinney, Neeraj Dhar, Zela Alexandria-Mae Martin

A DNA damage-inducible mutagenic gene cassette has been implicated in the emergence of drug resistance in Mycobacterium tuberculosis during anti-tuberculosis (TB) chemotherapy. However, the molecular composition and operation of the encoded 'mycobacterial ...

Elife Sciences Publ Ltd2023

Back-to-Africa introductions of Mycobacterium tuberculosis as the main cause of tuberculosis in Dar es Salaam, Tanzania

Jacques Fellay, Zhi Ming Xu

In settings with high tuberculosis (TB) endemicity, distinct genotypes of the Mycobacterium tuberculosis complex (MTBC) often differ in prevalence. However, the factors leading to these differences remain poorly understood. Here we studied the MTBC populat ...

PUBLIC LIBRARY SCIENCE2023

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

Preexisting Heterogeneity of Inducible Nitric Oxide Synthase Expression Drives Differential Growth of Mycobacterium tuberculosis in Macrophages

John McKinney, Ophélie Rutschmann, Chiara Toniolo

Mycobacterium tuberculosis infection is initiated by the inhalation and implantation of bacteria in the lung alveoli, where they are phagocytosed by macrophages. Even a single bacterium may be sufficient to initiate infection. Thereafter, the clinical outc ...

AMER SOC MICROBIOLOGY2022

Assessing and enhancing foldability in designed proteins

Bruno Emanuel Ferreira De Sousa Correia, Che Yang, Stéphane Rosset

Recent advances in protein-design methodology have led to a dramatic increase in reliability and scale. With these advances, dozens and even thousands of designed proteins are automatically generated and screened. Nevertheless, the success rate, particular ...

WILEY2022

An Oculus to Profile and Probe Target Engagement In Vivo: How T-REX Was Born and Its Evolution into G-REX

Chloé Rogg, Yimon Aye

Here we provide a personal account of innovation and design principles underpinning a method to interrogate precision electrophile signaling that has come to be known as "REX technologies". This Account is framed in the context of trying to improve methods ...

AMER CHEMICAL SOC2021

Microfluidics and cell-free synthetic biology in the development of new diagnostic and therapeutic platforms

Grégoire Michielin

In phenylketonuria, absence or malfunction of the phenylalanine hydroxylase enzyme results in toxic accumulation of phenylalanine in the body. An injectable recombinant enzyme therapy was recently approved and has the potential to improve the quality of li ...

EPFL2021

NICEdrug.ch, a workflow for rational drug design and systems-level analysis of drug metabolism

Vassily Hatzimanikatis, Noushin Hadadi, Jasmin Maria Hafner, Anush Chiappino-Pepe, Homa Mohammadi Peyhani

The discovery of a drug requires over a decade of intensive research and financial investments – and still has a high risk of failure. To reduce this burden, we developed the NICEdrug.ch resource, which incorporates 250,000 bioactive molecules, and studied ...

2021

Can Precision Electrophile Signaling Make a Meaningful and Lasting Impression in Drug Design?

Yimon Aye, Amogh Kulkarni

For several years, drugs with reactive electrophilic appendages have been developed. These units typically confer prolonged residence time of the drugs on their protein targets, and may assist targeting shallow binding sites and/or improving the drug-prote ...

WILEY-V C H VERLAG GMBH2022

FasR Regulates Fatty Acid Biosynthesis and Is Essential for Virulence of Mycobacterium tuberculosis

Stewart Cole, Claudia Sala

Mycobacterium tuberculosis, the etiologic agent of human tuberculosis, is the world's leading cause of death from an infectious disease. One of the main features of this pathogen is the complex and dynamic lipid composition of the cell envelope, which adap ...

Frontiers Media SA2020

Algorithms and flowchart for the design of synthetic biochemical networks

Homa Mohammadi Peyhani

New drugs are needed to assure effective therapies for previously untreated diseases, emerging diseases, and personalized medicine, but the process of drug development is complex, costly, and time-consuming. This is especially problematic considering that ...

EPFL2020

Synthesis and Structure-Activity Relationship Studies of C2-Modified Analogs of the Antimycobacterial Natural Product Pyridomycin

Stewart Cole, Ruben Hartkoorn, Anthony Vocat

A series of derivatives of the antimycobacterial natural product pyridomycin have been prepared with the C2 side chain attached to the macrocyclic core structure by a C-C single bond, in place of the synthetically more demanding enol ester double bond foun ...

AMER CHEMICAL SOC2020