Publications de Jonas Alfred Karl Wilbs

Combination of polycarboxybetaine coating and factor XII inhibitor reduces clot formation while preserving normal tissue coagulation during extracorporeal life support

Christian Heinis, Jonas Alfred Karl Wilbs

Blood contact with high surface area medical devices, such as dialysis and extracorporeal life support (ECLS), induces rapid surface coagulation. Systemic anticoagulation, such as heparin, is thus necessary to slow clot formation, but some patients suffer ...

ELSEVIER SCI LTD2021

In Vitro-Evolved Peptides Bind Monomeric Actin and Mimic Actin-Binding Protein Thymosin-β4

Christian Heinis, Davide Bertoldo, Raphael Johannes Gübeli, Jonas Alfred Karl Wilbs, Ganesh Kumar Mothukuri

Actin is the most abundant protein in eukaryotic cells and is key to many cellular functions. The filamentous form of actin (F-actin) can be studied with help of natural products that specifically recognize it, as for example fluorophore-labeled probes of ...

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

Engineered peptide macrocycles can inhibit matrix metalloproteinases with high selectivity

Christian Heinis, Jeremy Touati, Maola Khan Mohammad Golam, Michal Sabisz, Alice Baumann, Jonas Alfred Karl Wilbs, Xudong Kong, Kaycie Marie Butler

Matrix metalloproteinases (MMPs) are zinc‐dependent endopeptidases at the intersection of health and disease due to their involvement in processes such as tissue repair and immunity as well as cancer and inflammation. Because of the high structural conserv ...

2019

Improvement of a Closed Chest Porcine Myocardial Infarction Model by Standardization of Tissue and Blood Sampling Procedures

Jonas Alfred Karl Wilbs

Myocardial ischemia reperfusion (I/R) injury contributes to almost half of the necrotic area after myocardial infarction. To date there is no approved drug to prevent or reduce myocardial I/R injury. The study and understanding of the pathophysiological me ...

JOURNAL OF VISUALIZED EXPERIMENTS2018

Development of cyclic peptide inhibitors of coagulation factor XII and matrix metalloproteinase 2

Jonas Alfred Karl Wilbs

Peptides represent a promising molecular class for drug development. They combine several strengths of small molecules (e.g. efficient tissue diffusion, low immunogenicity and access to chemical synthesis) and key properties of biologics such as monoclonal ...

EPFL2018

Acylated heptapeptide binds albumin with high affinity and application as tag furnishes long-acting peptides

Christian Heinis, Alessandro Zorzi, Jonas Alfred Karl Wilbs, Simon Jan Middendorp, Kaycie Marie Butler

The rapid renal clearance of peptides in vivo limits this attractive platform for the treatment of a broad range of diseases that require prolonged drug half-lives. An intriguing approach for extending peptide circulation times works through a 'piggy-back' ...

Nature Research2017

Peptide macrocycle inhibitor of coagulation factor XII with subnanomolar affinity and high target selectivity

Christian Heinis, Jonas Alfred Karl Wilbs, Simon Jan Middendorp

Factor XII (FXII) is a plasma protease that has emerged in recent years as a potential target to treat or prevent pathological thrombosis, to inhibit contact activation in extracorporeal circulation, and to treat the swelling disorder hereditary angioedema ...

2017

Improving the binding affinity of in-vitro-evolved cyclic peptides by inserting atoms into the macrocycle backbone

Christian Heinis, Jonas Alfred Karl Wilbs, Simon Jan Middendorp

Cyclic peptides binding to targets of interest can be generated efficiently with powerful in vitro display techniques, such as phage display or mRNA display. The cyclic peptide libraries screened with these methods are generated by altering in a combinator ...

2016

Novel inhibitors of the enzyme activated factor xii (fxiia)

Christian Heinis, Vanessa Baeriswyl, Jonas Alfred Karl Wilbs, Simon Jan Middendorp

The present invention relates to a bicyclic inhibitor of the coagulation enzyme activated factor XII (FXIIa) comprising or consisting of the peptide (X1)(X2)(X3)n(X4)(X5)(X6)m(X7)(X9)l(X10)(X11)(X12)(X13)(X14)k(X15)(X16), wherein (X1) is present or absent ...

2016