Conjugate and Prodrug Strategies As Targeted Delivery Vectors for Antibiotics † † ‡ Ana V
Review Cite This: ACS Infect. Dis. XXXX, XXX, XXX−XXX pubs.acs.org/journal/aidcbc Signed, Sealed, Delivered: Conjugate and Prodrug Strategies as Targeted Delivery Vectors for Antibiotics † † ‡ Ana V. Cheng and William M. Wuest*, , † Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, United States ‡ Emory Antibiotic Resistance Center, Emory School of Medicine, 201 Dowman Drive, Atlanta, Georgia 30322, United States ABSTRACT: Innate and developed resistance mechanisms of bacteria to antibiotics are obstacles in the design of novel drugs. However, antibacterial prodrugs and conjugates have shown promise in circumventing resistance and tolerance mechanisms via directed delivery of antibiotics to the site of infection or to specific species or strains of bacteria. The selective targeting and increased permeability and accumu- lation of these prodrugs not only improves efficacy over unmodified drugs but also reduces off-target effects, toxicity, and development of resistance. Herein, we discuss some of these methods, including sideromycins, antibody-directed prodrugs, cell penetrating peptide conjugates, and codrugs. KEYWORDS: oligopeptide, sideromycin, antibody−antibiotic conjugate, cell penetrating peptide, dendrimer, transferrin inding new and innovative methods to treat bacterial F infections comes with many inherent challenges in addition to those presented by the evolution of resistance mechanisms. The ideal antibiotic is nontoxic to host cells, permeates bacterial cells easily, and accumulates at the site of infection at high concentrations. Narrow spectrum drugs are also advantageous, as they can limit resistance development and leave the host commensal microbiome undisturbed.1 However, various resistance mechanisms make pathogenic infections difficult to eradicate: Many bacteria respond to antibiotic pressure by decreasing expression of active transporters and porins2 and 3,4 Downloaded via EMORY UNIV on April 18, 2019 at 12:34:17 (UTC).
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