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The design, synthesis and evaluation of guanidinium-rich molecular transporters for the delivery of antibiotics and oligonucleotides
Huttner, Melanie Ann[Stanford, California] : [Stanford University], 2018.The delivery of cell-impenetrable therapeutic agents across biological barriers represents a challenging problem in the field of life science research and medicine. Many bacterial pathogens are inherently resistant to glycopeptide antibiotics such as vancomycin due to the antibiotic's relatively large size and mode of action, which requires actively growing cells. Recently, genetically-resistant vancomycin strains have emerged, adding to vancomycin's inefficaciousness against certain bacterial populations. The emergence and understanding of phenotypically and genetically resistant bacteria coupled to a declining pipeline of antibiotic development necessitates new strategies to combat bacterial infections. As part of a collaboration between the Wender and Cegelski labs, we have designed, synthesized and evaluated a novel vancomycin cell-penetrating peptide conjugate. We have shown that this new conjugate exhibits a unique mode of action compared to vancomycin, allowing it to be extremely effective against vancomycin-insensitive bacterial populations.
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