Publications de Patrick Andreas Gonschorek

Comparative analyses of Netherton syndrome patients and Spink5 conditional knock-out mice uncover disease-relevant pathways

Netherton syndrome (NS) is a rare skin disease caused by loss-of-function mutations in the serine peptidase inhibitor Kazal type 5 (SPINK5) gene. Disease severity and the lack of efficacious treatments call for a better understanding of NS mechanisms. Here ...

Nature Portfolio2024

Phage Display Selected Cyclic Peptide Inhibitors of Kallikrein-Related Peptidases 5 and 7 and Their In Vivo Delivery to the Skin

Luc Reymond, Christian Heinis, Alessandro Zorzi, Mischa Schüttel, Vanessa Carle, Tamara Maric, Patrick Andreas Gonschorek

Kallikrein-related peptidases 5 (KLK5) and 7 (KLK7) are serine proteases with homeostatic functions in the epidermis that play a critical role in Netherton syndrome (NS), a rare yet life-threatening genetic disorder that currently lacks specific treatment. ...

AMER CHEMICAL SOC2022

Novel inhibitors of kallikrein proteases and uses thereof

Christian Heinis, Alessandro Zorzi, Patrick Andreas Gonschorek

The present invention relates to a cyclic inhibitor of a kallikrein protease comprising or consisting of (I) the peptide (X)(X)(X)R(X)(X)(X)(X)(X)(X)(X)(X) (Formula (X)), wherein (X) is present or absent and, is prefer ...

2021

Novel inhibitors of kallikrein proteases and uses thereof

Christian Heinis, Alessandro Zorzi, Patrick Andreas Gonschorek

The present invention relates to a cyclic inhibitor of a kallikrein protease comprising or consisting of (I) the peptide (X1 (X2)(X3)R(X4)(X5)(X6)(X7)(X8)(X9)(X10)(X11) (Formula (X)), wherein (X1) is present or absent and, is preferably present, and if pre ...

2021

Cyclic peptide FXII inhibitor provides safe anticoagulation in a thrombosis model and in artificial lungs

Christian Heinis, Jonas Alfred Karl Wilbs, Simon Jan Middendorp, Xudong Kong, Christina Lamers, Patrick Andreas Gonschorek

Inhibiting thrombosis without generating bleeding risks is a major challenge in medicine. A promising solution may be the inhibition of coagulation factor XII (FXII), because its knock-out or inhibition in animals reduced thrombosis without causing abnorma ...

Nature Research2020

Development of Tissue Kallikrein Inhibitors for the Treatment of Netherton Syndrome

Patrick Andreas Gonschorek

There is currently no approved treatment for Netherton syndrome, which is a severe, genetic skin disease characterized by chronic inflammation and excessive peeling of the skin. Even though the molecular disease mechanism has been assigned to the unopposed ...

EPFL2019

Thiol-to-amine cyclization reaction enables screening of large libraries of macrocyclic compounds and the generation of sub-kilodalton ligands

Gerardo Turcatti, Jonathan Patrice Vesin, Christian Heinis, Van Manh Pham, Julien Bortoli Chapalay, Sangram Shivdas Kale, Xudong Kong, Milan Bergeron-Brlek, Patrick Andreas Gonschorek, João Miguel Franco Machado

Macrocyclic compounds are an attractive modality for drug development, but the limited availability of large, structurally diverse macrocyclic libraries hampers the discovery of leads. Here, we describe the discovery of efficient macrocyclization reactions ...

2019

Dual-controlled optogenetic system for the rapid down-regulation of protein levels in mammalian cells

Patrick Andreas Gonschorek

Optogenetic switches are emerging molecular tools for studying cellular processes as they offer higher spatiotemporal and quantitative precision than classical, chemical-based switches. Light-controllable gene expression systems designed to upregulate prot ...

Nature Research2018

The Swiss Summer School in Chemical Biology 2016 in brief

Raphaël Jovita De Matos, Jacques Saarbach, Patrick Andreas Gonschorek

Swiss Chemical Soc2016