Author:

Keywords:

Science & Technology, Physical Sciences, Chemistry, Multidisciplinary, Chemistry, CLICK-LINKED DNA, NUCLEOSIDE PHOSPHONATES, SEMISYNTHETIC ORGANISM, DUPLEX STRUCTURE, IN-VITRO, TRANSCRIPTION, REPLICATION, REPLACEMENT, THYMIDINE, EVOLUTION, Escherichia coli, Gene Expression, Models, Molecular, Nucleic Acid Conformation, Nucleic Acid Hybridization, Nucleic Acids, Oligonucleotides, Organophosphonates, 03 Chemical Sciences, General Chemistry, 34 Chemical sciences, 40 Engineering

Abstract:

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.