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Preparation of novel alkylated arginine derivatives suitable for click-cycloaddition chemistry and their incorporation into pseudosubstrate- and bisubstrate-based kinase inhibitors†
Jeroen van Ameijde,Alex J. Poot,Loek T. M. van Wandelen,Angelique E. M. Wammes,Rob Ruijtenbeek,Dirk T. S. Rijkers,Rob M. J. Liskamp
Organic & Biomolecular Chemistry Pub Date : 02/04/2010 00:00:00 , DOI:10.1039/B922928K
Abstract

Efficient strategies for the introduction of arginine residues featuring acetylene or azide moieties in their side chains are described. The substituents are introduced in a way that maintains the basicity of the guanidine moiety. The methodology can be used e.g. for non-invasive labeling of arginine-containing peptides. Its applicability is demonstrated by the introduction of ‘click’ handles into a Protein Kinase C (PKC) pseudosubstrate peptide, and the subsequent preparation and evaluation of a novel bisubstrate-based inhibitor based on such a peptide.

Graphical abstract: Preparation of novel alkylated arginine derivatives suitable for click-cycloaddition chemistry and their incorporation into pseudosubstrate- and bisubstrate-based kinase inhibitors
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