Colorimetric and Fluorescent Dual-Signal Chemosensor for Lysine and Arginine and Its Application to Detect Amines in Solid-Phase Peptide Synthesis

Abstract

Lysine (Lys) and arginine (Arg), as two of the most alkaline amino acids among 20 common amino acids, are closely involved in many vital biological processes and biomaterial synthesis. Abnormal levels of Lys and Arg can lead to various diseases. Although a limited number of fluorescent probes for Lys and Arg have been reported, many of them are not sensitive enough due to the moderate fluorescence signal and on-off mode. In addition, none of them were applied for detecting amine groups in solid-phase peptide synthesis. In this study, we designed and synthesized optical fluorescent probe 1 based on the benzoxadiazole fluorophore, which could undergo an accelerated hydrolysis reaction under basic conditions. Probe 1 revealed excellent selectivity toward alkaline Lys and Arg over other common amino acids with both fluorometric and colorimetric readouts. After treatment with Lys and Arg, probe 1 could emit a turn-on fluorescent response at 580 nm with a distinct color change from pink to yellow. The limit of detection for Lys and Arg was calculated to be 1.1 and 1.39 μM, respectively. We also successfully applied probe 1 for the visualization of Arg in living cells. Moreover, to the best of our knowledge, probe 1 provided the first fluorescent platform to detect -NH₂ groups in solid-phase synthesis of peptides with distinct fluorescent and colorimetric changes. We envision that the probe can provide an alternative method for the traditional Kaiser test.

Keywords: amide detection; arginine; dual-signal; lysine; solid-phase synthesis.