title: Development of a selective peptide macrocycle inhibitor of coagulation factor XII toward the generation of a safe antithrombotic therapy.
abstract: 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, we developed a potent inhibitor of FXII with more than 100-fold selectivity over related proteases. The highly selective peptide macrocycle is a promising candidate for the control of FXII activity in antithrombotic therapy and a valuable tool in hematology research.
authors.affiliation: Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne EPFL, CH-1015 Lausanne, Switzerland.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Baeriswyl
authors.forename: Sara
authors.initials: S
authors.lastname: Calzavarini
authors.forename: Christiane
authors.initials: C
authors.lastname: Gerschheimer
authors.forename: Philippe
authors.initials: P
authors.lastname: Diderich
authors.forename: Anne
authors.initials: A
authors.lastname: Angelillo-Scherrer
authors.forename: Christian
authors.initials: C
authors.lastname: Heinis
mesh_terms: D000595:Amino Acid Sequence; D055808:Drug Discovery; D004357:Drug Synergism; D005174:Factor XII / Q000037:antagonists & inhibitors*; D005343:Fibrinolytic Agents / Q000009:adverse effects* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D010456:Peptides, Cyclic / Q000009:adverse effects* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020842:Plasma Kallikrein / Q000037:antagonists & inhibitors; D012449:Safety
chemical_list: D005343:Fibrinolytic Agents; D010456:Peptides, Cyclic; D005174:Factor XII; D020842:Plasma Kallikrein