Evaluation of amphiphilic aminoglycoside-peptide triazole conjugates as antibacterial agents

Authors: Bera, Smritilekha; Zhanel, George G.; Schweizer, Frank; Bioorganic & Medicinal Chemistry; (2010); 10.1016/j.bmcl.2010.03.116

The solid- and solution-phase synthesis of amphiphilic aminoglycoside–peptide triazole conjugates (APTCs) accessed by copper(I)-catalyzed 1,3-dipolar cycloaddition reaction between a hydrophobic and ultrashort peptide-based alkyne and a neomycin B- or kanamycin A-derived azide is presented. Antibacterial evaluation demonstrates that the antibacterial potency is affected by the nature of the peptide component. Several APTCs exhibit superior activity against neomycin B- and kanamycin A-resistant strains when compared to their parent aminoglycoside while displaying reduced activity against neomycin B- and kanamycin A-susceptible strains.