Publications de Simon Jan Middendorp

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

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

Nature Research2020

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, Jonas Alfred Karl Wilbs, Vanessa Baeriswyl, 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