一种伊博霉素氚化方法可用于测量其核糖体结合。
A method for tritiation of iboxamycin permits measurement of its ribosomal binding.
机构信息
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Department of Pharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA; Center for Biomolecular Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
出版信息
Bioorg Med Chem Lett. 2023 Jul 15;91:129364. doi: 10.1016/j.bmcl.2023.129364. Epub 2023 Jun 7.
Hydrogen-tritium exchange is widely employed for radioisotopic labeling of molecules of biological interest but typically involves the metal-promoted exchange of sp-hybridized carbon-hydrogen bonds, a strategy that is not directly applicable to the antibiotic iboxamycin, which possesses no such bonds. We show that ruthenium-induced 2'-epimerization of 2'-epi-iboxamycin in HTO (200 mCi) of low specific activity (10 Ci/g, 180 mCi/mmol) at 80 °C for 18 h affords after purification tritium-labeled iboxamycin (3.55 µCi) with a specific activity of 53 mCi/mmol. Iboxamycin displayed an apparent inhibition constant (K) of 41 ± 30 nM towards Escherichia coli ribosomes, binding approximately 70-fold more tightly than the antibiotic clindamycin (K = 2.7 ± 1.1 µM).
氚-氢交换被广泛应用于生物感兴趣分子的放射性同位素标记，但通常涉及金属促进的 sp 杂化碳氢键的交换，这种策略不适用于抗生素伊博霉素，因为它没有这样的键。我们表明，在 80°C 下，用低比活度（10 Ci/g，180 mCi/mmol）的 HTO（200 mCi）对 2'-epi-伊博霉素进行钌诱导的 2'-差向异构化反应 18 小时后，经纯化可得到具有 53 mCi/mmol 的比活度的氚标记伊博霉素（3.55 µCi）。伊博霉素对大肠杆菌核糖体的表观抑制常数（K）为 41±30 nM，其结合亲和力比抗生素克林霉素（K=2.7±1.1 µM）高约 70 倍。
Zotero 插件