Abstract:

The interaction of sivelestat sodium（ONO-5046） and elastase was investigated using multispectral and molecular docking method. The fluorescence spectrum of the elastase is quenched by ONO-5046 and the mechanism of action is a static quenching process. ONO-5046 can bind with elastase to form 1∶1 complex. The thermodynamic parameters are calculated to beΔH < 0， ΔS < 0. Thermodynamic analysis suggests that hydrogen bonds and van der Waal′s forces are the main forces between ONO-5046 and elastase. ΔG<0 suggests that the interaction is a spontaneous process. The synchronous fluorescence spectrum， UV-Vis absorption and the circular dichroism spectra results show that the hydrophobicity of the environment around the amino acid residues in elastase decreases， the formation of ONO-5046 complex can influence some conformation changes of elastase， the proportion of α-helix structure decreases， the proportion of irregular crimp increases. The molecular docking simulation technique displays that a plurality of acyl structures， benzene rings and conjugated structures in the molecular skeleton of ONO-5046 provide the action site of the hydrogen bond and van der waals force， the three methyl groups on the end carbon are favorable for hydrophobicity， the electrolytic bridge is between oxygen anion and arignine of PPE. The results suggest that multiple forces exist between ONO-5046 and elastase system to form a stable compound， which inhibits the overexpression of elastase.

Key words: Sivelestat sodium, Elastase, Multispectroscopy, Molecular docking method