拉斯帕托霉素C的全合成及其抗菌作用机制的表征
Total Synthesis of Laspartomycin C and Characterization of Its Antibacterial Mechanism of Action.
作者信息
Kleijn Laurens H J, Oppedijk Sabine F, 't Hart Peter, van Harten Roel M, Martin-Visscher Leah A, Kemmink Johan, Breukink Eefjan, Martin Nathaniel I
机构信息
Department of Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
Membrane Biochemistry and Biophysics Group, Department of Chemistry, Utrecht University , Padualaan 8, 3584 CH Utrecht, The Netherlands.
出版信息
J Med Chem. 2016 Apr 14;59(7):3569-74. doi: 10.1021/acs.jmedchem.6b00219. Epub 2016 Mar 24.
Laspartomycin C is a lipopeptide antibiotic with activity against a range of Gram-positive bacteria including drug-resistant pathogens. We report the first total synthesis of laspartomycin C as well as a series of structural variants. Laspartomycin C was found to specifically bind undecaprenyl phosphate (C55-P) and inhibit formation of the bacterial cell wall precursor lipid II. While several clinically used antibiotics target the lipid II pathway, there are no approved drugs that act on its C55-P precursor.
拉斯帕托霉素C是一种脂肽类抗生素，对包括耐药病原体在内的多种革兰氏阳性菌具有活性。我们报道了拉斯帕托霉素C及其一系列结构变体的首次全合成。研究发现，拉斯帕托霉素C能特异性结合十一异戊烯基磷酸（C55-P）并抑制细菌细胞壁前体脂质II的形成。虽然几种临床使用的抗生素靶向脂质II途径，但尚无作用于其C55-P前体的获批药物。
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