How does hydroxyl introduction influence the double helical structure: the stabilization of an altritol nucleic acid:ribonucleic acid duplex.
Altritol nucleic acids (ANAs) are a promising new tool in the development of artificial small interfering ribonucleic acids (siRNAs) for therapeutical applications. To mimic the siRNA:messenger RNA (mRNA) interactions, the crystal structure of the ANA:RNA construct a(CCGUAAUGCC-P):r(GGCAUUACGG) was determined to 1.96 Å resolution which revealed the hybrid to form an A-type helix. As this A-form is a major requirement in the RNAi process, this crystal structure confirms the potential of altritol-modified siRNAs. Moreover, in the ANA strands, a new type of intrastrand interactions was found between the O2' hydroxyl group of one residue and the sugar ring O4' atom of the next residue. These interactions were further investigated by quantum chemical methods. Besides hydration effects, these intrastrand hydrogen bonds may also contribute to the stability of ANA:RNA duplexes.
Department of Chemistry, Katholieke Universiteit Leuven, Biomolecular Architecture and BioMacS, Celestijnenlaan 200F, B-3001 Leuven, Belgium.
Margriet
M
Ovaere
Jiri
J
Sponer
Judit E
JE
Sponer
Piet
P
Herdewijn
Luc
L
Van Meervelt
D006860:Hydrogen Bonding; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D012330:RNA, Double-Stranded / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000737:chemistry*; D013402:Sugar Alcohols / Q000737:chemistry*; D014867:Water / Q000737:chemistry
D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D013402:Sugar Alcohols; D014867:Water; C042890:altritol