Introducing Lasso Peptides as Molecular Scaffolds for Drug Design: Engineering of an Integrin Antagonist

Authors


  • Financial support from the Deutsche Forschungsgemeinschaft, the Fonds der Chemischen Industrie, the LOEWE program of the State of Hesse, and the BMBF project MobiTUM 01EZ0826 is gratefully acknowledged. We would like to thank Wera Collisi for excellent technical assistance with tube formation and proliferation assays.

Abstract

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Tightening the noose: Lasso peptides are a class of stable bacterial peptides with unique characteristics that encourage their application in drug design. Epitope grafting of the integrin binding motif RGD onto the lasso structure of microcin J25 converts the knotted peptide into a nanomolar integrin antagonist (see picture). Engineered lasso peptides can therefore be used for pharmacophore presentation.

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