Picomolar Inhibition of Plasmepsin V, an Essential Malaria Protease, Achieved Exploiting the Prime Region
Fig 4
Separation and activity of the synthetized diastereoisomers.
(A) Analytical RP-HPLC chromatogram of Compound 2 crude reaction mixture. (B) Superimposition of RP-HPLC traces of Compound 2a (red) and Compound 2b (green) after preparative purification. Inset: enlargement of the two separated diastereoisomers. (C) Inhibitory activity of PmV activity by Compounds 2a and 2b (Fig 2 panel b). Bars represent SEM. (D-F) NMR analysis. (D) Key cross-peaks for the 2D NMR ROESY spectrum. (E) The relevant section of 2D NMR ROESY spectrum of Compound 3a. (F) Absolute stereo-structure of the active diastereoisomer. Configuration at the carbons was determined through J-based configuration analysis. Selected cross-peaks detected in the 2D NMR ROESY spectrum supported the stereo-chemical assignment.