Overcoming AlbD Protease Resistance and Improving Potency: Synthesis and Bioactivity of Antibacterial Albicidin Analogues with Amide Bond Isosteres

Abstract

Albicidin is a potent antibacterial oligoaromatic peptide that is susceptible to the protease AlbD, a resistance factor. This potentially restricts the use of albicidin as a drug. To overcome this obstacle, we synthesized and evaluated six analogues with isosteric replacement of the key amide link. Protease stability was established while maintaining the antibacterial activity, including three analogues with up to eight times higher activity compared with the natural albicidin.