Synthesis and base pairing properties of 1',5'-anhydro-L-hexitol nucleic acids (L-HNA).
Oligonucleotides composed of 1',5'-anhydro-arabino-hexitol nucleosides belonging to the L series (L-HNA) were prepared and preliminarily studied as a novel potential base-pairing system. Synthesis of enantiopure L-hexitol nucleotide monomers equipped with a 2'-(N(6)-benzoyladenin-9-yl) or a 2'-(thymin-1-yl) moiety was carried out by a de novo approach based on a domino reaction as key step. The L oligonucleotide analogues were evaluated in duplex formation with natural complements as well as with unnatural sugar-modified oligonucleotides. In many cases stable homo- and heterochiral associations were found. Besides T(m) measurements, detection of heterochiral complexes was unambiguously confirmed by LC-MS studies. Interestingly, circular dichroism measurements of the most stable duplexes suggested that L-HNA form left-handed helices with both D and L oligonucleotides.
D'Alonzo
Daniele
D
Dipartimento di Chimica Organica e Biochimica, Università Federico II, Napoli, via Cinthia 4, 80126 Napoli, Italy.
Van Aerschot
Arthur
A
Guaragna
Annalisa
A
Palumbo
Giovanni
G
Schepers
Guy
G
Capone
Stefania
S
Rozenski
Jef
J
Herdewijn
Piet
P
D001089:Arabinose / Q000737:chemistry*; D020029:Base Pairing; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009696:Nucleic Acids / Q000138:chemical synthesis* / Q000378:metabolism; D009705:Nucleosides / Q000138:chemical synthesis* / Q000378:metabolism*; D009841:Oligonucleotides / Q000737:chemistry* / Q000378:metabolism; D013237:Stereoisomerism
D009696:Nucleic Acids; D009705:Nucleosides; D009841:Oligonucleotides; D004247:DNA; D001089:Arabinose