报告题目：Synthesis and Genetic Selection of a Xenobiotic Nucleic Acid with the Acyclic Phosphonate Backbone
报 告 人：罗敏 博士（比利时鲁汶大学）
Dr. Min Luo held his PhD in medicinal chemistry from KU Leuven in September 2017 and was a postdoctoral researcher at the same university for 2 years. His research was about the synthesis and biomedical applications of nucleosides, nucleotides, and nucleic acids. He and his colleagues tried to develop an artificial genetic information system. He also identified a series of novel nucleoside phosphonates and the corresponding amidate prodrugs with potent activities against viruses including the hepatitis B virus, the human immunodeficiency virus, and herpesviruses.
Significant effort has been devoted in recent years in developing synthetic genetic systems (XNAs) into functional polymers as well as means to encode novel traits in living cells for various purposes. However, for in vivo applications, it is crucial that XNAs are metabolically accessible by the action of cellular enzymes from suitably activated monomers and are able to form relatively stable homoduplexes in order to induce folding processes, while being orthogonal. A chiral acyclic-phosphonate backbone [(S)-ZNA] for its potential to function as XNA was investigated. This modification showed the expected properties, as the double-stranded (S)-ZNA was found to adopt an atypical left-handed geometry in preliminary study, the acyclic phosphonate diphosphate monomers were recognized as substrates by E. coli polymerase I as well as being imported into E. coli cells equipped with an algal nucleotide transporter. (S)-ZNA also showed signs of in vivo recognition. In addition, it is the first example of recognition of an acyclic oligonucleotide by a cellular polymerase in vivo.