Synthesis of Vitamin B<sub>12</sub>-Antibiotic Conjugates with Greatly Improved Activity against Gram-Negative Bacteria
Sheng Zhao, Zhi‐Peng Wang, Xumei Wen, Siyu Li, Guoxing Wei, Jian Guo, Yun He
Abstract
There is an urgent need to discover new antibiotics and improve the efficacy of known antibiotics against Gram-negative bacteria. “Trojan horse” conjugates are novel and promising antibiotics. Herein we report the design and synthesis of vitamin-B12–ampicillin conjugates, which exhibited more than 500 times improved activity against Escherichia coli compared with ampicillin itself. Our studies demonstrate that the vitamin-B12 uptake pathway could be employed for effective antibiotic delivery and efficacy enhancement.
Topics & Concepts
ChemistryGramAntibioticsBacteriaGram-negative bacteriaConjugateGram-positive bacteriaVitamin bMicrobiologyVitaminCombinatorial chemistryEscherichia coliBiochemistryBiologyMathematicsGeneticsGeneMathematical analysisPorphyrin Metabolism and DisordersBiochemical and Molecular ResearchFolate and B Vitamins Research