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

Autor: Jonas Wilbs, Xu-Dong Kong, Simon J. Middendorp, Raja Prince, Alida Cooke, Caitlin T. Demarest, Mai M. Abdelhafez, Kalliope Roberts, Nao Umei, Patrick Gonschorek, Christina Lamers, Kaycie Deyle, Robert Rieben, Keith E. Cook, Anne Angelillo-Scherrer, Christian Heinis

Publikováno v: Nature Communications, Vol 11, Iss 1, Pp 1-13 (2020)

Inhibiting thrombosis without inducing bleeding is a major challenge for anticoagulant agents. Here the authors describe a synthetic FXIIa inhibitor able to efficiently prevent thrombosis in mice and suppress coagulation in artificial lungs in rabbit

Externí odkaz: https://doaj.org/article/1f9ddb75be1e4a398c1ff63698dcaa1b

Peptide Macrocycle Inhibitor of Coagulation Factor XII with Subnanomolar Affinity and High Target Selectivity

Autor: Claudia Quarroz, Simon J. Middendorp, Anne Angelillo-Scherrer, Jonas Wilbs, Sara Calzavarini, Christian Heinis

Publikováno v: Middendorp, Simon Jan; Wilbs, Jonas; Quarroz, Claudia; Calzavarini, Sara; Angelillo-Scherrer, Anne; Heinis, Christian (2017). Peptide macrocycle inhibitor of coagulation factor XII with subnanomolar affinity and high target selectivity. Journal of medicinal chemistry, 60(3), pp. 1151-1158. American Chemical Society 10.1021/acs.jmedchem.6b01548

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 angi

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::57b9d0c5fa1bfd965b84539a430b9aff
https://doi.org/10.1021/acs.jmedchem.6b01548

Relative positioning of classical benzodiazepines to the ?2-subunit of GABAA receptors

Autor: Dirk Trauner, Simon J. Middendorp, Michael Pangerl, Erwin Sigel, Evelyn Hurni, Matthias Schönberger, Marco Stein

Publikováno v: ACS chemical biology

GABAA receptors are the major inhibitory neurotransmitter receptors in the brain. Benzodiazepine exert their action via a high affinity-binding site at the α/γ subunit interface on some of these receptors. Diazepam has sedative, hypnotic, anxiolyti

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d1d9175ae44ccf9891c66801dbf4ae7f

Azo-Propofols: Photochromic Potentiators of GABAAReceptors

Autor: Ervin Pejo, Stuart A. Forman, Simon J. Middendorp, Valentina Carta, Marco Stein, Dirk Trauner, Erwin Sigel, Douglas E. Raines

Publikováno v: Angewandte Chemie
Angewandte Chemie (International ed. in English)

Shine and rise! GABA(A) receptors are ligand-gated chloride ion channels that respond to γ-aminobutyric acid (GABA), which is the major inhibitory neurotransmitter of the mammalian central nervous system. Azobenzene derivatives of propofol, such as

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b4756cbc2fb5b7547ff3c253993dbd97
https://doi.org/10.1002/ange.201205475

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

Autor: Christian Heinis, Jonas Wilbs, Simon J. 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 comb

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e8cbbbb1d3871c56a42be5742e64e8ad
https://infoscience.epfl.ch/record/227015