title: Artificially expanded genetic information system: a new base pair with an alternative hydrogen bonding pattern.
abstract: To support efforts to develop a 'synthetic biology' based on an artificially expanded genetic information system (AEGIS), we have developed a route to two components of a non-standard nucleobase pair, the pyrimidine analog 6-amino-5-nitro-3-(1'-beta-D-2'-deoxyribofuranosyl)-2(1H)-pyridone (dZ) and its Watson-Crick complement, the purine analog 2-amino-8-(1'-beta-D-2'-deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)-one (dP). These implement the pyDDA:puAAD hydrogen bonding pattern (where 'py' indicates a pyrimidine analog and 'pu' indicates a purine analog, while A and D indicate the hydrogen bonding patterns of acceptor and donor groups presented to the complementary nucleobases, from the major to the minor groove). Also described is the synthesis of the triphosphates and protected phosphoramidites of these two nucleosides. We also describe the use of the protected phosphoramidites to synthesize DNA oligonucleotides containing these AEGIS components, verify the absence of epimerization of dZ in those oligonucleotides, and report some hybridization properties of the dZ:dP nucleobase pair, which is rather strong, and the ability of each to effectively discriminate against mismatches in short duplex DNA.
authors.affiliation: Foundation for Applied Molecular Evolution, 1115 NW 4th Street, Gainesville, FL 32601, USA.
authors.forename: Zunyi
authors.initials: Z
authors.lastname: Yang
authors.forename: Daniel
authors.initials: D
authors.lastname: Hutter
authors.forename: Pinpin
authors.initials: P
authors.lastname: Sheng
authors.forename: A Michael
authors.initials: AM
authors.lastname: Sismour
authors.forename: Steven A
authors.initials: SA
authors.lastname: Benner
mesh_terms: D020137:Base Pair Mismatch; D020029:Base Pairing; D003853:Deoxyribonucleosides / Q000737:chemistry*; D006860:Hydrogen Bonding; D007536:Isomerism; D009691:Nucleic Acid Denaturation; D009693:Nucleic Acid Hybridization; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry*; D009711:Nucleotides / Q000138:chemical synthesis / Q000737:chemistry; D009841:Oligonucleotides / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000737:chemistry; D011728:Pyridones / Q000737:chemistry*; D013696:Temperature; D014227:Triazines / Q000737:chemistry*
chemical_list: C515831:2-amino-8-(1'-(2'-deoxyribofuranosyl))imidazo(1,2-a)-1,3,5-triazin-4(8H)-one; C515830:6-amino-5-nitro-3-(1'-(2'-deoxyribofuranosyl))-2(1H)-pyridone; D003853:Deoxyribonucleosides; D009705:Nucleosides; D009711:Nucleotides; D009841:Oligonucleotides; D009943:Organophosphorus Compounds; D011728:Pyridones; D014227:Triazines; C434331:phosphoramidite