Preparation of novel alkylated arginine derivatives suitable for click-cycloaddition chemistry and their incorporation into pseudosubstrate- and bisubstrate-based kinase inhibitors.
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.
van Ameijde
Jeroen
J
Medicinal Chemistry and Chemical Biology, Faculty of Science, Utrecht University, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands.
Poot
Alex J
AJ
van Wandelen
Loek T M
LT
Wammes
Angelique E M
AE
Ruijtenbeek
Rob
R
Rijkers
Dirk T S
DT
Liskamp
Rob M J
RM
D000595:Amino Acid Sequence; D001120:Arginine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D003500:Cyclization; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D047428:Protein Kinase Inhibitors / Q000031:analogs & derivatives* / Q000138:chemical synthesis
D010455:Peptides; D047428:Protein Kinase Inhibitors; D001120:Arginine