title: Solid-phase synthesis of mimosine tetrapeptides and their inhibitory activities on neuraminidase and tyrosinase.
abstract: 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 IC(50) 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-A(1)-A(2)-A(3)) 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 IC(50) of 18.3 ± 0.5 μM. The kinetic studies showed that all of the synthesized peptides inhibited neuraminidase noncompetitively with K(i) values ranging from 1.9 -to 7.2 μM. These results suggest that mimosine could be used as a source of bioactive compounds and may have possibilities in the design of drugs as neuraminidase and tyrosinase inhibitors.
authors: Department of Bioscience and Biotechnology, The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima 890-0065, Japan.
authors: Atul
authors: A
authors: Upadhyay
authors: Jamnian
authors: J
authors: Chompoo
authors: Nozomi
authors: N
authors: Taira
authors: Masakazu
authors: M
authors: Fukuta
authors: Shinichi
authors: S
authors: Gima
authors: Shinkichi
authors: S
authors: Tawata
mesh_terms: D000998:Antiviral Agents; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007887:Fabaceae / Q000737:chemistry; D007700:Kinetics; D008898:Mimosine / Q000032:analysis / Q000737:chemistry* / Q000494:pharmacology; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors*; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D012621:Seasons; D060327:Solid-Phase Synthesis Techniques
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D008898:Mimosine; D014442:Monophenol Monooxygenase; D009439:Neuraminidase