Phosphinate, sulfonate, and sulfonamidate dipeptides as potential inhibitors of Escherichia coli aminopeptidase N

In an effort to prepare novel inhibitors of bacterial aminopeptidase N (PepN), the phosphinate, propenylphosphinate, decylphosphinate, sulfonate, and sulfonamidate analogs of Ala–Ala were synthesized and tested as inhibitors. Phosphinate 1 was shown to inhibit PepN with a Ki of 10 μM, and propenylphosphinate 2 and decylphosphinate 3 inhibited PepN with a Ki of ca. 1 μM. Sulfonate and sulfonamidate analogs did not inhibit PepN.