Expedient discovery of fluorogenic amino acid-based probes via one-pot palladium-catalysed arylation of tyrosine†

Abstract

To overcome the limitations of using large extrinsic chromophores for biological imaging, fluorescent unnatural α-amino acids have been widely adopted as intrinsic peptidic probes. Although various classes have been successfully utilised for imaging applications, novel amino acid probes readily prepared through operationally simple synthetic methodology are still required. Here, we report a new approach for the synthesis of unnatural α-amino acids via a one-pot process involving activation and palladium-catalysed arylation of tyrosine. Rapid access to a small library of novel α-amino acids has allowed the discovery of a dimethylaminobiphenyl analogue that displays strong charge transfer-based fluorescent properties and is both solvatochromic and pH sensitive with a significant hypsochromic shift in emission under acidic conditions. The imaging potential of the dimethylaminobiphenyl α-amino acid was demonstrated via its application as a FRET donor in a novel decapeptide substrate for monitoring and evaluating the kinetics of a serine protease.