Cochrane Stephen A, Li Xuefeng, He Sisi, Yu Min, Wu Min, Vederas John C
Department of Chemistry, University of Alberta , Edmonton, Alberta, T6G 2G2, Canada.
Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences , Grand Forks, North Dakota 58203-9037, United States.
J Med Chem. 2015 Dec 24;58(24):9779-85. doi: 10.1021/acs.jmedchem.5b01578. Epub 2015 Dec 4.
A series of tridecaptin-antibiotic conjugates were synthesized and evaluated for in vitro and in vivo activity against Gram-negative bacteria. Covalently linking unacylated tridecaptin A1 (H-TriA1) to rifampicin, vancomycin, and erythromycin enhanced their activity in vitro but not by the same magnitude as coadministration of the peptide and these antibiotics. The antimicrobial activities of the conjugates were retained in vivo, with the H-TriA1-erythromycin conjugate proving a more effective treatment of Klebseilla pneumoniae infections in mice than erythromycin alone or in combination with H-TriA1.
合成了一系列十三肽抗生素缀合物，并对其针对革兰氏阴性菌的体外和体内活性进行了评估。将未酰化的十三肽A1（H-TriA1）与利福平、万古霉素和红霉素共价连接，增强了它们的体外活性，但增强幅度不如该肽与这些抗生素联合给药时大。缀合物的抗菌活性在体内得以保留，其中H-TriA1-红霉素缀合物在治疗小鼠肺炎克雷伯菌感染方面比单独使用红霉素或红霉素与H-TriA1联合使用更有效。
