Cystine Knot Peptides with Tuneable Activity and Mechanism

Abstract: Knottins are topologically complex peptides that are stabilised by a cystine knot and have exceptionally diverse functions, including protease inhibition. However, approaches for tuning their activity in situ are limited. Here, we demonstrate separate approaches for tuning the activity of knottin protease inhibitors using light or streptavidin. We show that the inhibitory activity and selectivity of an engineered knottin can be controlled with light by activating a second mode of action that switches the inhibitor ON against new targets. Guided by a knottin library screen, we also identify a position in the inhibitor's binding loop that permits insertion of a biotin tag without impairing activity. Using streptavidin, biotinylated knottins with nanomolar affinity can be switched OFF in activity assays, and the anticoagulant activity of a factor XIIa inhibitor can be rapidly switched OFF in human plasma. Our findings expand the scope of engineered knottins for precisely controlling protein function.

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch

Verweise und Beziehungen

• Erschienen in: Cystine Knot Peptides with Tuneable Activity and Mechanism ; day:11 ; month:03 ; year:2022 ; extent:1 ; Angewandte Chemie ; (11.03.2022) (gesamt 1)

Beteiligte, Orts- und Zeitangaben

• Urheber: Li, Choi Yi ; Rehm, Fabian B. H. ; Yap, Kuok ; Zdenek, Christina N. ; Harding, Maxim D. ; Fry, Bryan G. ; Durek, Thomas ; Craik, David ; de Veer, Simon J.

Weitere Informationen

• DOI: 10.1002/ange.202200951
• URN: urn:nbn:de:101:1-2022031214082793039933
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 15.08.2025, 07:33 MESZ