Phosphonamidate and phosphothioate dipeptides as potential inhibitors of VanX

In an effort to prepare novel inhibitors of VanX, N-[(1-aminoethyl)hydroxyphosphinyl]- -alanine 1 and S-[(aminoethyl)hydroxyphosphinyl]-thiolacetic acid 2 were synthesized and evaluated as inhibitors of VanX. Phosphonamidate 1 was shown to be a partial competitive inhibitor of VanX with a Ki of 36±3 μM, and phosphothioate 2 was shown not to inhibit VanX.