A facile method for monitoring solid-phase peptide synthesis and for N-terminal modification of peptides: synthesis of short peptides for imaging specific cells

A simple method for naked-eye detection of free amine groups during solid-phase peptide synthesis is reported. The technique involves base-catalyzed cyclization of 2-(2-oxo-2H-acenaphthylene-1-ylidene)-malononitrile ( 1 ) and subsequent oxidative substitution of aryl moiety by free amine group present at the N-terminus of the peptide chain that leads to the formation of a chromophore, which distinguishes the deprotected peptide chain from the protected one. The reaction is fast, does not require heating, and allows N-terminal modification of peptides suitable for imaging specific cells. Graphical Abstract Base catalyzed cyclization of 2-(2-oxo-2H-acenaphthylene-1-ylidene)-malononitrile and subsequent oxidative substitution by free amine group leads to the formation of a chromophore, which permits naked-eye detection of the deprotected peptide on resin support.