North Carolina State University
In situ Oxidation of N-Phenylglycinyl Peptides for Oxime Bond Formation at Neutral pH
Oxime bond formation between a-oxo aldehydes and aminooxy groups has demonstrated widespread utility for the selective functionalization of biomolecules. Current methods often rely on aniline catalysis to increase reaction rates at neutral pH via formation of a protonated aniline-Schiff base intermediate.
Here, we report an alternate route to access this reactive intermediate via in situ oxidation of N-phenylglycinyl peptide substrates under mild aqueous conditions in the absence of catalysts. We demonstrate that the reaction conditions to trigger the tandem oxidation/oxime ligation depend on the electronics of the N-phenyglycine residue, are compatible with sensitive residues, forexample Met, and exhibit improved orthogonality towards aldehydes.