Catalysis of Hydrazone and Oxime Peptide Ligation by Arginine

Hydrazone and oxime peptide ligations
are catalyzed by arginine. The catalysis is assisted intramolecularly
by the side-chain guanidinium group. Hydrazone ligation in the presence
of arginine proceeds efficiently in phosphate buffer at neutral pH
but is particularly powerful in bicarbonate/CO2 buffer.
In addition to acting as a catalyst, arginine prevents the aggregation
of proteins during ligation. With its dual properties as a nucleophilic
catalyst and a protein aggregation inhibitor, arginine hydrochloride
is a useful addition to the hydrazone/oxime ligation toolbox.