Protein‐Templated Formation of an Inhibitor of the Blood Coagulation Factor Xa through a Background‐Free Amidation Reaction

Abstract: Protein‐templated reactions enable the target‐guided formation of protein ligands from reactive fragments, ideally with no background reaction. Herein, we investigate the templated formation of amides. A nucleophilic fragment that binds to the coagulation factor Xa was incubated with the protein and thirteen differentially activated dipeptides. The protein induced a non‐catalytic templated reaction for the phenyl and trifluoroethyl esters; the latter was shown to be a completely background‐free reaction. Starting from two fragments with millimolar affinity, a 29 nm superadditive inhibitor of factor Xa was obtained. The fragment ligation reaction was detected with high sensitivity by an enzyme activity assay and by mass spectrometry. The reaction progress and autoinhibition of the templated reaction by the formed ligation product were determined, and the structure of the protein–inhibitor complex was elucidated.

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: Protein‐Templated Formation of an Inhibitor of the Blood Coagulation Factor Xa through a Background‐Free Amidation Reaction ; volume:56 ; number:13 ; year:2017 ; pages:3718-3722 ; extent:5 ; Angewandte Chemie / International edition. International edition ; 56, Heft 13 (2017), 3718-3722 (gesamt 5)

Contributors, Places and Time

• Creator: Jaegle, Mike ; Steinmetzer, Torsten ; Rademann, Jörg

Further information

• DOI: 10.1002/anie.201611547
• URN: urn:nbn:de:101:1-2022092008510587537635
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:30 AM CEST