4 research outputs found
Hachimoji DNA and RNA: A genetic system with eight building blocks
Reported here are DNA and RNA-like systems built from eight (hachi-) nucleotide letters (-moji) that form four orthogonal pairs. This synthetic genetic biopolymer meets the structural requirements needed to support Darwinism, including a polyelectrolyte backbone, predictable thermodynamic stability, and stereoregular building blocks that fit a Schrödinger aperiodic crystal. Measured thermodynamic parameters predict the stability of hachimoji duplexes, allowing hachimoji DNA to double the information density of natural terran DNA. Three crystal structures show that the synthetic building blocks do not perturb the aperiodic crystal seen in the DNA double helix. Hachimoji DNA was then transcribed to give hachimoji RNA in the form of a functioning fluorescent hachimoji aptamer. These results expand the scope of molecular structures that might support life, including life throughout the cosmos
A mild and efficient method for the preparation of 5'-dimethoxytrityl-2'-deoxy-nucleoside using poly(4-vinylpyridine)-costyrene
370-371<span style="font-size:13.5pt;mso-bidi-font-size:6.5pt;
font-family:HiddenHorzOCR;mso-hansi-font-family:" times="" new="" roman";mso-bidi-font-family:="" hiddenhorzocr;mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:="" ar-sa"="">5'-O-4,4'-Dimethoxytrityl-2'-deoxynucleosides have been synthesized in high yield by the
reaction of 2'-deoxynucleosides with 4, 4'-dimethoxytrityl chloride in
acetonitrile using poly (4- vinylpyridine)-costyrene (styrene 10%).</span
Synthesis and Enzymology of 2′-Deoxy-7-deazaisoguanosine Triphosphate and Its Complement: A Second Generation Pair in an Artificially Expanded Genetic Information System
As with natural nucleic acids, pairing
between artificial nucleotides
can be influenced by tautomerism, with different placements of protons
on the heterocyclic nucleobase changing patterns of hydrogen bonding
that determine replication fidelity. For example, the major tautomer
of isoguanine presents a hydrogen bonding <i>donor</i>–<i>donor</i>–<i>acceptor</i> pattern complementary
to the <i>acceptor</i>–<i>acceptor</i>–<i>donor</i> pattern of 5-methylisocytosine. However, in its minor
tautomer, isoguanine presents a hydrogen bond <i>donor</i>–<i>acceptor</i>–<i>donor</i> pattern
complementary to thymine. Calculations, crystallography, and physical
organic experiments suggest that this tautomeric ambiguity might be
“fixed” by replacing the N-7 nitrogen of isoguanine
by a CH unit. To test this hypothesis, we prepared the triphosphate
of 2′-deoxy-7-deazaiso-guanosine and used it in PCR to estimate
an effective tautomeric ratio “seen” by <i>Taq</i> DNA polymerase. With 7-deazaisoguanine, fidelity-per-round was ∼92%.
The analogous PCR with isoguanine gave a lower fidelity-per-round
of ∼86%. These results confirm the hypothesis with polymerases,
and deepen our understanding of the role of minor groove hydrogen
bonding and proton tautomerism in both natural and expanded genetic
“alphabets”, major targets in synthetic biology
Synthesis and Enzymology of 2′-Deoxy-7-deazaisoguanosine Triphosphate and Its Complement: A Second Generation Pair in an Artificially Expanded Genetic Information System
As with natural nucleic acids, pairing
between artificial nucleotides
can be influenced by tautomerism, with different placements of protons
on the heterocyclic nucleobase changing patterns of hydrogen bonding
that determine replication fidelity. For example, the major tautomer
of isoguanine presents a hydrogen bonding <i>donor</i>–<i>donor</i>–<i>acceptor</i> pattern complementary
to the <i>acceptor</i>–<i>acceptor</i>–<i>donor</i> pattern of 5-methylisocytosine. However, in its minor
tautomer, isoguanine presents a hydrogen bond <i>donor</i>–<i>acceptor</i>–<i>donor</i> pattern
complementary to thymine. Calculations, crystallography, and physical
organic experiments suggest that this tautomeric ambiguity might be
“fixed” by replacing the N-7 nitrogen of isoguanine
by a CH unit. To test this hypothesis, we prepared the triphosphate
of 2′-deoxy-7-deazaiso-guanosine and used it in PCR to estimate
an effective tautomeric ratio “seen” by <i>Taq</i> DNA polymerase. With 7-deazaisoguanine, fidelity-per-round was ∼92%.
The analogous PCR with isoguanine gave a lower fidelity-per-round
of ∼86%. These results confirm the hypothesis with polymerases,
and deepen our understanding of the role of minor groove hydrogen
bonding and proton tautomerism in both natural and expanded genetic
“alphabets”, major targets in synthetic biology