Synthesis of crosslinking amino acids by click chemistry

Crosslinking amino acids are naturally existing protein crosslinkers. Herein, we described the synthesis of several novel bis-amino acids constituted of serine, alanine, lysine, and tyrosine with click chemistry. The Huisgen 1,3-dipolar cycloadditions between azido- and alkyne-functionalized amino acids can be easily realized in the presence of catalytic amount of CuSO4 and Na ascorbate. In addition, fluorescent bis-amino acid derivatives have also been prepared using anthracene, fluorescein, and benzothiadiazole as fluorophores. With symmetrical bis-alkyne benzothiadiazole, it was possible to synthesize asymmetrical derivative bearing two different amino acid moieties.