Designing Hybrid Antibiotic Peptide Conjugates To Cross Bacterial Membranes

Authors: Deshayes, Stephanie; Xian, Wujing; Schmidt, Nathan W.; Kordbacheh, Shadi; Lieng, Juelline; Wang, Jennifer; Zarmer, Sandra; Germain, Samantha St.; Voyen, Laura; Thulin, Julia; Wong, Gerard C. L.; Kasko, Andrea M.; Bioconjugate Chemistry; (2017); 10.1021/acs.bioconjchem.6b00725

We design hybrid antibiotic peptide conjugates that can permeate membranes. Integration of multiple components with different functions into a single molecule is often problematic, due to competing chemical requirements for different functions and to mutual interference. By examining the structure of antimicrobial peptides (AMPs), we show that it is possible to design and synthesize membrane active antibiotic peptide conjugates (MAAPCs) that synergistically combine multiple forms of antimicrobial activity, resulting in unusually strong activity against persistent bacterial strains.