title: Biophysics of Artificially Expanded Genetic Information Systems. Thermodynamics of DNA Duplexes Containing Matches and Mismatches Involving 2-Amino-3-nitropyridin-6-one (Z) and Imidazo[1,2-a]-1,3,5-triazin-4(8H)one (P).
abstract: Synthetic nucleobases presenting non-Watson-Crick arrangements of hydrogen bond donor and acceptor groups can form additional nucleotide pairs that stabilize duplex DNA independent of the standard A:T and G:C pairs. The pair between 2-amino-3-nitropyridin-6-one 2'-deoxyriboside (presenting a {donor-donor-acceptor} hydrogen bonding pattern on the Watson-Crick face of the small component, trivially designated Z) and imidazo[1,2-a]-1,3,5-triazin-4(8H)one 2'-deoxyriboside (presenting an {acceptor-acceptor-donor} hydrogen bonding pattern on the large component, trivially designated P) is one of these extra pairs for which a substantial amount of molecular biology has been developed. Here, we report the results of UV absorbance melting measurements and determine the energetics of binding of DNA strands containing Z and P to give short duplexes containing Z:P pairs as well as various mismatches comprising Z and P. All measurements were done at 1 M NaCl in buffer (10 mM Na cacodylate, 0.5 mM EDTA, pH 7.0). Thermodynamic parameters (ΔH°, ΔS°, and ΔG°37) for oligonucleotide hybridization were extracted. Consistent with the Watson-Crick model that considers both geometric and hydrogen bonding complementarity, the Z:P pair was found to contribute more to duplex stability than any mismatches involving either nonstandard nucleotide. Further, the Z:P pair is more stable than a C:G pair. The Z:G pair was found to be the most stable mismatch, forming either a deprotonated mismatched pair or a wobble base pair analogous to the stable T:G mismatch. The C:P pair is less stable, perhaps analogous to the wobble pair observed for C:O6-methyl-G, in which the pyrimidine is displaced into the minor groove. The Z:A and T:P mismatches are much less stable. Parameters for predicting the thermodynamics of oligonucleotides containing Z and P bases are provided. This represents the first case where this has been done for a synthetic genetic system.
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland , College Park, Maryland 20742, United States.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Foundation for Applied Molecular Evolution , 13709 Progress Boulevard, No. 7, Alachua, Florida 32615, United States.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hoshika
authors.affiliation: Celadon Laboratories , 6525 Belcrest Road, Hyattsville, Maryland 20782, United States.
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Peterson
authors.affiliation: Foundation for Applied Molecular Evolution , 13709 Progress Boulevard, No. 7, Alachua, Florida 32615, United States.
authors.forename: Myong-Jung
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Foundation for Applied Molecular Evolution , 13709 Progress Boulevard, No. 7, Alachua, Florida 32615, United States.|Firebird Biomolecular Sciences LLC , 13709 Progress Boulevard, No. 17, Alachua, Florida 32615, United States.
authors.forename: Steven A
authors.identifier: 0000-0002-3318-9917
authors.initials: SA
authors.lastname: Benner
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland , College Park, Maryland 20742, United States.
authors.forename: Jason D
authors.identifier: 0000-0001-5060-4724
authors.initials: JD
authors.lastname: Kahn
mesh_terms: D020137:Base Pair Mismatch / Q000235:genetics / Q000502:physiology; D020029:Base Pairing / Q000235:genetics; D001703:Biophysics / Q000379:methods*; D006860:Hydrogen Bonding; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D009841:Oligonucleotides / Q000737:chemistry / Q000235:genetics; D011725:Pyridines / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: C000594399:2-amino-3-nitropyridin-6-one; D009841:Oligonucleotides; D011725:Pyridines