Concept

Bleeding diathesis

Publications associées (11)

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

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

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 ...

2020

From Patients to Platelets and Back Again: Pharmacological Approaches to Glycoprotein VI, a Thrilling Antithrombotic Target with Minor Bleeding Risks

Nikolaos Stergiopoulos, Augusto Martins Lima

Despite significant advances in the treatment of thrombogenic diseases, antiplatelet therapies are still associated with a high bleeding risk. Consequently, potential benefits of preventing thromboembolic events by pharmacological agents need to be balance ...

GEORG THIEME VERLAG KG2019

Development of cyclic peptide inhibitors of coagulation factor XIa for safer anticoagulation

Vanessa Carle

Hemostasis is a complex physiological process responsible for the prevention of blood loss caused by vascular injury. The dysregulation of this delicate mechanism can lead to thromboembolic diseases, the leading cause of death worldwide. Anticoagulants are ...

EPFL2019

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

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

Microdevice for Sedimentation-based Separation of Blood Microsamples at the Point of Collection

David Forchelet

Laboratory blood testing plays a central role in current diagnostics and therapeutical decisions. Thus, errors have a direct impact on care quality and cost. The majority of errors occur in the pre-analytical phase, when samples are collected, stored and p ...

EPFL2017

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

A Synthetic Factor XIIa Inhibitor Blocks Selectively Intrinsic Coagulation Initiation

Christian Heinis, Shiyu Chen, Alessandro Zorzi, Vanessa Baeriswyl, Luca Bologna

Coagulation factor XII (FXII) inhibitors are of interest for the study of the protease in the intrinsic coagulation pathway, for the suppression of contact activation in blood coagulation assays, and they have potential application in antithrombotic therap ...

American Chemical Society2015

Identification of target-binding peptide motifs by high-throughput sequencing of phage-selected peptides

Christian Heinis, Inmaculada Rentero Rebollo, Vanessa Baeriswyl, Michal Sabisz

High-throughput sequencing was previously applied to phage-selected peptides in order to gain insight into the abundance and diversity of isolated peptides. Herein we developed a procedure to efficiently compare the sequences of large numbers of phage-sele ...

Oxford Univ Press2014

Development of a selective peptide macrocycle inhibitor of coagulation factor XII toward the generation of a safe antithrombotic therapy

Christian Heinis, Philippe Diderich, Vanessa Baeriswyl

Inhibition of coagulation factor XII (FXII) activity represents an attractive approach for the treatment and prevention of thrombotic diseases. The few existing FXII inhibitors suffer from low selectivity. Using phage display combined to rational design, w ...

2013

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