Studies on the Chemical Modification of Arginine: I. THE REACTION OF 1,2-CYCLOHEXANEDIONE WITH ARGININE AND ARGINYL RESIDUES OF PROTEINS

Abstract

Abstract The guanido group of arginine condenses with 1,2-cyclohexanedione in alkaline aqueous medium to form a new α-amino acid. The product(1,2-cyclohexanedione-arginine) was shown by independent synthesis to be N5-(4-oxo-1,3-diazaspiro[4.4]non - 2 - ylidene) - l - ornithine. At hydroxide concentrations of 0.2 n or higher, this was the principal product, and the reaction with free arginine and with the arginyl residues of model proteins was completed in 3 hours. At lower base concentration or with salmine at high base concentrations, a heterogeneous mixture of ninhydrin-positive products was observed. The reaction appears to be specific for the guanido group. Peptide maps of tryptic digests of 1,2-cyclohexanedione-treated chains of hemoglobin showed blocking of hydrolysis at arginyl bonds with no change in positions of tryptic peptides not adjacent to arginyl residues.