Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224, Warsaw, Poland.
Centre of New Technologies, University of Warsaw, Banacha 2c, 02-097, Warsaw, Poland.
Chemistry. 2018 Dec 12;24(70):18772-18778. doi: 10.1002/chem.201804304. Epub 2018 Nov 15.
Gram-negative bacteria develop specific systems for the uptake of scarce nutrients, including vitamin B . These uptake pathways may be utilized for the delivery of biologically relevant molecules into cells. Indeed, it was recently reported that vitamin B transported an antisense peptide nucleic acid (PNA) into Escherichia coli and Salmonella Typhimurium cells. The present studies indicate that the conjugation site of PNA to vitamin B has an impact on PNA transport into bacterial cells. Toward this end, a specifically designed PNA oligomer has been tethered at various positions of vitamin B (central Co, R -OH, c and e amide chains, meso position, and at the hydroxy group of cobinamide) by using known or newly developed methodologies and tested for the uptake of the synthesized conjugates by E. coli. Compounds in which the PNA oligonucleotide was anchored at the R -OH position were transported more efficiently than that of other compounds tethered at the peripheral positions around the corrin ring. Of importance is the fact that, contrary to mammalian organisms, E. coli also takes up cobinamide, which is an incomplete corrinoid. This selectivity opens up ways to fight bacterial infections.
革兰氏阴性细菌会发展出特定的系统来摄取稀缺的营养物质，包括维生素 B12。这些摄取途径可用于将具有生物学意义的分子递送到细胞内。事实上，最近有报道称，维生素 B12 可将反义肽核酸（PNA）输送到大肠杆菌和沙门氏菌 Typhimurium 细胞内。本研究表明，PNA 与维生素 B12 的连接位点会影响 PNA 向细菌细胞内的转运。为此，通过已知或新开发的方法，将专门设计的 PNA 寡核苷酸连接到维生素 B12 的不同位置（中央 Co、R -OH、c 和 e 酰胺链、meso 位以及 cobinamide 的羟基）上，并通过大肠杆菌来测试合成缀合物的摄取情况。与连接在围绕卟啉环的外围位置的其他化合物相比，锚定在 R -OH 位置的 PNA 寡核苷酸的化合物的转运效率更高。重要的是，与哺乳动物不同，大肠杆菌还能摄取 cobinamide，这是一种不完全的类咕啉。这种选择性为对抗细菌感染开辟了道路。
