The stability of DNA duplexes is dependent on a complex array of hydrogen bonding among amino and carbonyl groups of the heteroaromatic bases and surrounding water molecules, as well as base stacking interactions. Duplex stability can be significantly increased by adding a further hydrogen bond to a base pair, for example by modifying the regular A-T base pair containing two hydrogen bonds with the 2-amino-A-T base pair containing three hydrogen bonds. Another popular strategy is to use a hydrophobic natural or unnatural modification to displace water molcecules from the duplex to generate a stabilizing effect. Examples of this strategy are the use of 5-Me-dC or 5-propynyl-dU. With three hydrogen bonds, the C-G base pair has a big effect on duplex stability. A strategy to normalize the effects of C-G and A-T base pairing is to destabilize the C-G base pair to the same strength as the A-T base pair by partially blocking one hydrogen bond using N4-Et-C.
A variety of modified nucleobases are available for use in the study of DNA duplex stability modification.
Glen Research offers a wide range of products for research in selective duplex stabilization.
Synthetic oligonucleotides with covalently-attached CDPI3 have enhanced DNA affinity and have improved the hybridization properties of sequence-specific DNA probes.
Spermine phosphoramidite is used to produce oligospermine-oligonucleotide conjugates - Zip Nucleic Acids (ZNA®) Oligos.
New cap structures allow for the preparation of hybridization probes with increased affinity for complementary sequences.
Oligonucleotides containing LNA exhibit unprecedented thermal stabilities towards complementary DNA and RNA, which allows excellent mismatch discrimination.