Binding interactions between enantiomeric α-aminophosphonate derivatives and tobacco mosaic virus coat protein

Tobacco mosaic virus (TMV) is an important plant virus that can cause considerable crop loss. Our group synthesized a series of enantiomeric alpha-aminophosphonate derivatives with high anti-TMV activities. The activity of (R)-diphenyl-1-(4-methylbenzothiazole-2-amino)-1-(thiphene-2-yl)-methylphosphonate (Q-R) was found to be superior to that of (S)-diphenyl-1-(4-methyl benzothiazole-2-amino)-1-(thiphene-2-yl)-methylphosphonate (Q-S). However, the mechanism for inhibition of the R-isomer (Q-R) of infection activity is not clear. Thus, we studied the interactions between Q-R and Q-S and TMV by using TMV coat proteins (CP) as a potential target for fluorescence spectroscopy, isothermal titration calorimetry, microscale thermophoresis, and molecular docking. Arg90 was found to play a major role in the interaction of Q-R with TMV CP, as demonstrated by the interaction experiments and the results of molecular modeling. The substitution of arginine with glycine resulted in a mutant that was significantly less sensitive to Q-R. These results indicate that Q-R undermines the structural stability of the TMV R90G virus particle by binding with Arg90, eventually leading to the loss of the virus' ability for infection. (C) 2016 Elsevier B.V. All rights reserved.