Publications related to Cysteine protease

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

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

Cysteine-Cysteine Cross-Conjugation of both Peptides and Proteins with a Bifunctional Hypervalent Iodine-Electrophilic Reagent

Jérôme Waser, Stefano Nicolai, Abhaya Kumar Mishra

Peptide and protein bioconjugation sees ever-growing applications in the pharmaceutical sector. Novel strategies and reagents that can address the chemo- and regioselectivity issues inherent to these biomolecules, while delivering stable and functionalizab ...

2023

Bacterial matrix metalloproteases and serine proteases contribute to the extra-host inactivation of enteroviruses in lake water

Tamar Kohn, Virginie Bachmann

Enteroviruses are ubiquitous contaminants of surface waters, yet their fate in presence of microbial congeners is poorly understood. In this work, we investigated the inactivation of Echovirus-11 (E11) and Coxsackievirus-A9 (CVA9) by bacteria isolated from ...

2022

Amphiphilic Iodine(III) Reagents for the Lipophilization of Peptides in Water

Jérôme Waser, Durga Prasada Rao Hari, Romain Gaëtan Tessier, Abhaya Kumar Mishra

We report the functionalization of cysteine residues with lipophilic alkynes bearing a silyl group or an alkyl chain using amphiphilic ethynylbenziodoxolone reagents (EBXs). The reactions were carried out in buffer (pH 6 to 9), without organic co-solvent o ...

Wiley-VCH Verlag GmbH2021

Ethynylation of Cysteine Residues: From Peptides to Proteins in Vitro and in Living Cells

Jérôme Waser, Romain Gaëtan Tessier, Charlotte Marie Sornay, Raj Kumar Nandi

Current approaches to introduce terminal alkynes for bioorthogonal reactions into biomolecules still present limitations in terms of either reactivity, selectivity, or adduct stability. We present a method for the ethynylation of cysteine residues based on ...

Wiley-VCH Verlag GmbH2020

The mRNA-Binding Protein HuR Is a Kinetically-Privileged Electrophile Sensor

Yimon Aye, Jesse Poganik, Yi Zhao, Alexandra Krina Van Hall-Beauvais

The key mRNA-binding proteins HuR and AUF1 are reported stress sensors in mammals. Intrigued by recent reports of sensitivity of these proteins to the electrophilic lipid prostaglandin A2 and other redox signals, we here examined their sensing abilities to ...

2020

Thioredoxin-Related Transmembrane Proteins: TMX1 and Little Brothers TMX2, TMX3, TMX4 and TMX5

Maurizio Molinari

The endoplasmic reticulum (ER) is site of synthesis and maturation of membrane and secretory proteins in eukaryotic cells. The ER contains more than 20 members of the Protein Disulfide Isomerase (PDI) family. These enzymes regulate formation, isomerization ...

2020

Protease-activation using anti-idiotypic masks enables tumor specificity of a folate receptor 1-T cell bispecific antibody

Henning Paul-Julius Stahlberg

T-cell bispecific antibodies (TCBs) crosslink tumor and T-cells to induce tumor cell killing. While TCBs are very potent, on-target off-tumor toxicity remains a challenge when selecting targets. Here, we describe a protease-activated anti-folate receptor 1 ...

Nature Research2020

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

Getting the Right Grip? How Understanding Electrophile Selectivity Profiles Could Illuminate Our Understanding of Redox Signaling

Yimon Aye, Lingxi Wang

Recent Advances: Herein, we focus on the first step of this process, electrophile sensing. Electrophile sensing is typically a deceptively simple reaction between the thiol of a protein cysteine, of which there are around 200,000 in the human proteome, and ...

MARY ANN LIEBERT, INC2020

The metalloprotease ADAMTS4 generates N-truncated A4-x species and marks oligodendrocytes as a source of amyloidogenic peptides in Alzheimer's disease

Patrick Fraering, Mitko Dimitrov, Hermeto Gerber, Sandra Lehmann

Brain accumulation and aggregation of amyloid- (A) peptides is a critical step in the pathogenesis of Alzheimer's disease (AD). Full-length A peptides (mainly A1-40 and A1-42) are produced through sequential proteolytic cleavage of the amyloid precursor pr ...

SPRINGER2019

More Than Black or White: Melanization and Toll Share Regulatory Serine Proteases in Drosophila

Bruno Lemaitre, Jan Paul Dudzic, Mark Austin Hanson, Igor Iatsenko

The melanization response is an important defense mechanism in arthropods. This reaction is mediated by phenoloxidases (POs), which are activated by complex extracellular serine protease (SP) cascades. Here, we investigate the role of SPs in the melanizati ...

2019

Anthrax toxin requires ZDHHC5-mediated palmitoylation of its surface-processing host enzymes

Françoise Gisou van der Goot Grunberg, Oksana Andrei Sergeeva

The protein acyl transferase ZDHHC5 was recently proposed to regulate trafficking in the endocytic pathway. Therefore, we explored the function of this enzyme in controlling the action of bacterial toxins. We found that ZDHHC5 activity is required for two ...

National Academy of Sciences2019

Discovery of novel competitive dihydropteridine reductase inhibitors via high throughput screening and their effect on metabolic pterin balance of fibroblast

Yann Mathieu Pierson

The development of tool compounds for the study of the tetrahydrobiopterin (BH4) metabolic network perturbation is of interest especially in the case of oxidative and nitrosative stress genesis. A semisynthetic FRET sensor was engineered in order to study ...

EPFL2018

Novel compartment-specific biosensors reveal a complementary subcellular distribution of bioactive Furin and PC7

Pierpaolo Ginefra

Proprotein Convertases (PCs) constitute a family of serine proteases that activate various hormones, growth factors and cell adhesion molecules by mediating endoproteolytic cleavage of their secreted inactive precursors during their transit in the secret ...

EPFL2018

Structure-Based Drug Design and Characterization of Sulfonyl-Piperazine Benzothiazinone Inhibitors of DprE1 from Mycobacterium tuberculosis

Stewart Cole, Anthony Vocat, Jérémie Piton, Shi-Yan Caroline Foo, Andréanne Lupien

Macozinone (MCZ) is a tuberculosis (TB) drug candidate that specifically targets the essential flavoenzyme DprE1, thereby blocking synthesis of the cell wall precursor decaprenyl phosphoarabinose (DPA) and provoking lysis of Mycobacterium tuberculosis. As ...

AMER SOC MICROBIOLOGY2018

Fluorescent Benzothiazinone Analogues Efficiently and Selectively Label Dpre1 in Mycobacteria and Actinobacteria

Paul Joseph Dyson, Stewart Cole, John McKinney, Neeraj Dhar, Thierry Laroche, Jérémie Piton, Joao Pedro De Almeida Neres, Raphael Christopher Sommer, Raju Mukherjee

Benzothiazinones (BTZ) are highly potent bactericidal inhibitors of mycobacteria and the lead compound, BTZ043, and the optimized drug candidate, PBTZ169, have potential for the treatment of tuberculosis. Here, we exploited the tractability of the BTZ scaf ...

2018

Palmitoylation mediates membrane association of hepatitis E virus ORF3 protein and is required for infectious particle secretion

Françoise Gisou van der Goot Grunberg, Laurence Gouzi Abrami, Johann Mauron, Joël Oppliger, Maxime Matter, Noémie Oechslin

Hepatitis E virus (HEV) is a positive-strand RNA virus encoding 3 open reading frames (ORF). HEV ORF3 protein is a small, hitherto poorly characterized protein involved in viral particle secretion and possibly other functions. Here, we show that HEV ORF3 p ...

PUBLIC LIBRARY SCIENCE2018

Transition metal clusters on h-BN/Rh(111) : surface interaction and catalytic activity

Hamed Achour

The main aim of this dissertation is to study the catalytic aspects of very small transition metal clusters supported on h-BN/Rh(111). The catalytic reactions of interest were ammonia synthesis and CO oxidation on mass selected and soft landed iron and pla ...

EPFL2017