title: Optimization of interstrand hydrophobic packing interactions within unnatural DNA base pairs.
abstract: As part of an effort to expand the genetic alphabet, we have evaluated a large number of predominantly hydrophobic unnatural base pairs. We now report the synthesis and stability of unnatural base pairs formed between simple phenyl rings modified at different positions with methyl groups. Surprisingly, several of the unnatural base pairs are virtually as stable as a natural base pair in the same sequence context. The results show that neither hydrogen-bonding nor large aromatic surface area are required for base pair stability within duplex DNA and that interstrand interactions between small aromatic rings may be optimized for both stability and selectivity. These smaller nucleobases are not expected to induce the distortions in duplex DNA or at the primer terminus that seem to limit replication of larger unnatural base pairs, and they therefore represent a promising approach to the expansion of the genetic alphabet.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Matsuda
authors.forename: Floyd E
authors.initials: FE
authors.lastname: Romesberg
mesh_terms: D020029:Base Pairing; D002942:Circular Dichroism; D004247:DNA / Q000138:chemical synthesis / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009705:Nucleosides / Q000737:chemistry; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D009705:Nucleosides; D009841:Oligonucleotides; D004247:DNA