Solid-Phase Synthesis of Mimosine Tetrapeptides and Their Inhibitory Activities on Neuraminidase and Tyrosinase

Neuraminidase is a rational target for influenza inhibition, and the search for neuraminidase inhibitors has been intensified. Mimosine, a nonprotein amino acid, was for the first time identified as a neuraminidase inhibitor with an IC50 of 9.8 ± 0.2 μM. It was found that mimosine had slow, time-dependent competitive inhibition against the neuraminidase. Furthermore, a small library of mimosine tetrapeptides (M–A1–A2–A3) was synthesized by solid-phase synthesis and was assayed to evaluate their neuraminidase and tyrosinase inhibitory properties. Most of the tetrapeptides showed better activities than mimosine. Mimosine–FFY was the best compound, and it exhibited 50% neuraminidase inhibition at a low micromolar range of 1.8 ± 0.2 μM, whereas for tyrosinase inhibition, it had an IC50 of 18.3 ± 0.5 μM. The kinetic studies showed that all of the synthesized peptides inhibited neuraminidase noncompetitively with Ki values ranging from 1.9 -to 7.2 μM. These results suggest that mimosine could be used as a sourc...