Fig. 1: Characterization of TFV ProTides.

a Synthesis of phenyl alanine and alanine derivatizing promoieties. b Conjugation of the amino acid esters to activated monophenyl TFV to form M1TFV and M2TFV prodrugs. c Aqueous and octanol solubility of M1TFV and M2TFV demonstrate the decreased aqueous solubility of M1TFV (green) and M2TFV (orange), and increased octanol solubility compared to TAF (blue). Values reported are the mean ± SEM of three replicates. d FT-IR Absorption bands at 2,844 and 2,912 cm⁻¹ illustrate the asymmetric and symmetric C-H stretches from the long chain fatty acid. e An overlay of the proton NMR spectra confirmed the synthesis of M1TFV (below) and M2TFV (above). Specifically, the triplet peak at 0.87 ppm and multiplets at 1.21–1.35 ppm correspond to the terminal methyl and methylene protons of the docosyl ester on M1TFV, respectively. Chemical shifts at 7.04−7.38 ppm represent the aryl and phenylalanine masking promoieties. For M2TFV, the triplet at 0.87 ppm and multiplets at 1.20–1.38 ppm correspond to the terminal methyl and methylene protons of the docosyl ester, respectively. Chemical shifts at 6.99, 7.10, 7.14, 7.21, and 7.31 ppm represent the aryl masking promoiety. a−e Experiments were repeated independently five times with equivalent results.