Synthesis and pairing properties of alpha-tricyclo-DNA.
We describe the synthesis of the phosphoramidite building blocks of alpha-tricyclo-DNA (alpha-tc-DNA) covering all four natural bases, starting from the already known corresponding alpha-tc-nucleosides. These building blocks were used for the preparation of three alpha-tc-oligonucleotide 10-mers representing a homopurine, a homopyrimidine, and a mixed purine/pyrimidine base sequence. The base-pairing properties with complementary parallel and antiparallel oriented DNA and RNA were studied by UV-melting analysis and CD spectroscopy. We found that alpha-tc-DNA binds preferentially to parallel nucleic acid complements through Watson-Crick duplex formation, with a preference for RNA over DNA. In comparison with natural DNA, alpha-tc-DNA shows equal to enhanced affinity to RNA and also pairs to antiparallel DNA or RNA complements, although with much lower affinity. In the mixed-base sequence these antiparallel duplexes are of the reversed Watson-Crick type, while in the homopurine/homopyrimidine sequences Hoogsteen and/or reversed Hoogsteen pairing is observed. Antiparallel duplex formation of two alpha-tc-oligonucleotides was also observed, although the thermal stability of this duplex was surprisingly low. The base-pairing properties of alpha-tc-DNA are discussed in the context of alpha-DNA, alpha-RNA, and alpha-LNA.
Scheidegger
Simon P
SP
Department of Chemistry & Biochemistry, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland.
Leumann
Christian J
CJ
D020029:Base Pairing; D001483:Base Sequence; D002942:Circular Dichroism; D004247:DNA / Q000138:chemical synthesis / Q000737:chemistry* / Q000528:radiation effects; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry* / Q000528:radiation effects; D009943:Organophosphorus Compounds / Q000737:chemistry*; D012313:RNA / Q000737:chemistry*; D014466:Ultraviolet Rays
D009841:Oligonucleotides; D009943:Organophosphorus Compounds; C434331:phosphoramidite; D012313:RNA; D004247:DNA