Invading Escherichia coli Genetics with a Xenobiotic Nucleic Acid Carrying an Acyclic Phosphonate Backbone (ZNA).
Min LuoElisabetta GroazMatheus FroeyenValérie PezoFaten JaziriPiotr LeonczakGuy SchepersJef RozenskiPhilippe MarlièrePiet HerdwijnPublished in: Journal of the American Chemical Society (2019)
A synthetic orthogonal polymer embracing a chiral acyclic-phosphonate backbone [(S)-ZNA] is presented that uniquely adds to the emerging family of xenobiotic nucleic acids (XNAs). (S)-ZNA consists of reiterating six-atom structural units and can be accessed in few synthetic steps from readily available phophonomethylglycerol nucleoside (PMGN) precursors. Comparative thermal stability experiments conducted on homo- and heteroduplexes made of (S)-ZNA are described that evince its high self-hybridization efficiency in contrast to poor binding of natural complements. Although preliminary and not conclusive, circular dichroism data and dynamic modeling computations provide support to a left-handed geometry of double-stranded (S)-ZNA. Nonetheless, PMGN diphosphate monomers were recognized as substrates by Escherichia coli (E. coli) polymerase I as well as being imported into E. coli cells equipped with an algal nucleotide transporter. A further investigation into the in vivo propagation of (S)-ZNA culminated with the demonstration of the first synthetic nucleic acid with an acyclic backbone that can be transliterated to DNA by the E. coli cellular machinery.
Keyphrases
- nucleic acid
- escherichia coli
- induced apoptosis
- biofilm formation
- electronic health record
- machine learning
- cell cycle arrest
- signaling pathway
- magnetic resonance imaging
- staphylococcus aureus
- mass spectrometry
- pseudomonas aeruginosa
- binding protein
- transcription factor
- ionic liquid
- cell free
- cell death
- circulating tumor