title: Solution structure and conformational dynamics of deoxyxylonucleic acids (dXNA): an orthogonal nucleic acid candidate.
abstract: Orthogonal nucleic acids are chemically modified nucleic acid polymers that are unable to transfer information with natural nucleic acids and thus can be used in synthetic biology to store and transfer genetic information independently. Recently, it was proposed that xylose-DNA (dXNA) can be considered to be a potential candidate for an orthogonal system. Herein, we present the structure in solution and conformational analysis of two self-complementary, fully modified dXNA oligonucleotides, as determined by CD and NMR spectroscopy. These studies are the initial experimental proof of the structural orthogonality of dXNAs. In aqueous solution, dXNA duplexes predominantly form a linear ladderlike (type-1) structure. This is the first example of a furanose nucleic acid that adopts a ladderlike structure. In the presence of salt, an equilibrium exists between two types of duplex form. The corresponding nucleoside triphosphates (dXNTPs) were synthesized and evaluated for their ability to be incorporated into a growing DNA chain by using several natural and mutant DNA polymerases. Despite the structural orthogonality of dXNA, DNA polymerase β mutant is able to incorporate the dXNTPs, showing DNA-dependent dXNA polymerase activity.
authors.affiliation: Laboratory of Medicinal Chemistry, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium.
authors.forename: Mohitosh
authors.initials: M
authors.lastname: Maiti
authors.forename: Vanessa
authors.initials: V
authors.lastname: Siegmund
authors.forename: Mikhail
authors.initials: M
authors.lastname: Abramov
authors.forename: Eveline
authors.initials: E
authors.lastname: Lescrinier
authors.forename: Helmut
authors.initials: H
authors.lastname: Rosemeyer
authors.forename: Mathy
authors.initials: M
authors.lastname: Froeyen
authors.forename: Amutha
authors.initials: A
authors.lastname: Ramaswamy
authors.forename: Arnout
authors.initials: A
authors.lastname: Ceulemans
authors.forename: Andreas
authors.initials: A
authors.lastname: Marx
authors.forename: Piet
authors.initials: P
authors.lastname: Herdewijn
mesh_terms: D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008958:Models, Molecular; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009696:Nucleic Acids / Q000737:chemistry*; D016376:Oligonucleotides, Antisense / Q000737:chemistry*; D014994:Xylose / Q000737:chemistry*
chemical_list: D009696:Nucleic Acids; D016376:Oligonucleotides, Antisense; D014994:Xylose; D004259:DNA-Directed DNA Polymerase