3CAPS - a structural AP-site analogue as a tool to investigate DNA base excision repair.

Abasic sites (AP-sites) are frequent DNA lesions, arising by spontaneous base hydrolysis or as intermediates of base excision repair (BER). The hemiacetal at the anomeric centre renders them chemically reactive, which presents a challenge to biochemical and structural investigation. Chemically more stable AP-site analogues have been used to avoid spontaneous decay, but these do not fully recapitulate the features of natural AP-sites.

Strand invasion properties and serum stability of alpha-tricyclo-DNA.

beta-tricyclo DNA (tcDNA) is a third generation antisense oligonucleotide developed and studied extensively in our laboratory. We recently became interested in the pairing properties of its alpha-anomeric form and observed parallel duplex formation with natural DNA and RNA. These duplexes were of the same level of thermal stability as their natural counterparts.

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.