Crystal structures of deprotonated nucleobases from an expanded DNA alphabet

Matsuura, Mariko F.; Kim, Hyo Joong; Takahashi, Daisuke; Abboud, Khalil A.; Benner, Steven A.

doi:10.1107/s2053229616017071

Cited by 5 publications

(6 citation statements)

References 52 publications

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“…11 Thus, it has been used for chemical fine-tuning of artificial DNA and RNA in synthetic biology. [12][13][14][15] TPI heterosynthon (R 2 2 (12) graph-set motif) 16,17 is very robust and reliable, and has been used in the construction of supramolecular assemblies since many years. 18 Rods, tapes and cyclic hexamers (rosettes) have been prepared using this synthon in the ADA/DAD complexes of cyanuric acid and melamine with a (1:1) stoichiometry.…”

Section: Introductionmentioning

confidence: 99%

“…Among chemical variations of nucleic acids that allow chemists to harness and reprogram the cellular machinery, the diversification of the nucleobase structure due to the halogen substitution in uracil and the amino substitution in adenine creates additional DNA/RNA base pairs, modifies the thermal stability, and increases the specificity of the hosting duplexes. − Indeed, from one side recently several studies have been focused on the importance of halogen bonding (XB) in directing the conformation of DNA containing halonucleobases. − From the other side, the ability of 2-aminosubstituted adenine to form ADA/DAD hydrogen bonding patterns (three-point interactions, TPI) significantly increases the base-pair stability retaining the structural integrity of the nucleic acid nanostructure . Thus, it has been used for chemical fine-tuning of artificial DNA and RNA in synthetic biology. − …”

Section: Introductionmentioning

confidence: 99%

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Multifacial Recognition in Binary and Ternary Cocrystals from 5-Halouracil and Aminoazine Derivatives

Portalone

2018

Crystal Growth & Design

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A systematic analysis using single crystal X-ray diffraction was performed to explore the role exerted by potential intercomponent proton-transfer reactions in the supramolecular structures of A-B cocrystals formed by 5-haloderivatives of uracil (A) coupled with 2-aminoadenine simulants (aminoazines, B). Twelve new heterodimers were synthesized in different stoichiometry and cocrystallized by solvent co-grinding followed by solution crystallization. In the binary cocrystals, uracil or 1-methyluracil with halide modification at the 5 position (F, Cl, Br, I) were coupled with aminoaromatic N-heterocycles (melamine, 2,4,6-triaminopyrimidine, 2,6-diaminopyridine) as multivalent site for pyrimidine nucleobase recognition. The crystallographic analysis showed that, next to the expected neutral three-point hydrogen bonds (TPI), ionized TPI, favored by A → B proton transfer, can be used for WC multifacial recognition. Noteworthy, the formation of the charged TPI, which depends on the acid/base properties of the components, takes always place between the more acidic site of the 5halonucleobases (N3 atom) and the more basic site (imino N atom) of 2,4,6-triaminopyrimidine or 2,6diaminopyridine, and melamine recognition unit results to be insufficiently basic to accept a proton. The general ability of pyrimidine nucleobases to provide electron donating groups to halogen bonding has been confirmed in seven cocrystals containing the 5-chloro, 5-bromo or 5-iododerivatives coupled with melamine or 2,4,6-triaminopyrimidine. Considerations of the relative acidities of coformers A and of the relative basicities of coformers B allowed us to design and characterize by single-crystal X-ray diffraction the first ternary pyrimidine nucleobase-containing cocrystal based on the JANUS-WEDGE concept: the nucleobase-Janus-nucleobase (1:1:1) triad showing a 2,4,6-triamino pyrimidine molecule wedged via neutral and ionized TPI between the 5-fluorouracil/1-methyluracil pair in reverse WC fashion. ABSTRACTA systematic analysis using single crystal X-ray diffraction was performed to explore the role exerted by potential intercomponent proton-transfer reactions in the supramolecular structures of A-B cocrystals formed by 5-haloderivatives of uracil (A), coupled with 2-aminoadenine simulants (aminoazines, B). Twelve new heterodimers were synthesized in different stoichiometry and cocrystallized by solvent co-grinding followed by solution crystallization. In the binary cocrystals, uracil or 1-methyluracil with halide modification at the 5 position (F, Cl, Br, I) were coupled with amino-aromatic N-heterocycles (melamine, 2,4,6-triaminopyrimidine, 2,6-diaminopyridine) as multivalent site for pyrimidine nucleobase recognition. The crystallographic analysis showed that, next to the expected neutral three-point hydrogen bonds (TPI), ionized TPI, favored by A → B proton transfer, can be used for WC multifacial recognition. Noteworthy, the formation of the charged TPI, which depends on the acid/base properties of the components, takes always place between ...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Multifacial Recognition in Binary and Ternary Cocrystals from 5-Halouracil and Aminoazine Derivatives

Portalone

2018

Crystal Growth & Design

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“…S4; S5). These calculations started with the geometry of the Z -:Z pairing observed in the structure of the crystal formed from the aminonitropyridone heterocycle alone 25 . The electron distributions in the HOMO and LUMO of the hypothetic Z:Z pair are partially separated, leading to stabilization energy of 1.93 kcal/mol for the Z:Z pair.…”

Section: Discussionmentioning

confidence: 99%

“…Some non-canonical structures with non-standard nucleobases might involve interactions between their protonated and deprotonated forms, analogous to the protonated cytosine required for the i-motif in standard DNA. For example, we recently solved a crystal structure where 6-amino-5-nitropyrid-2-one (the heterocycle in the added nucleotide known as "Z") crystallizes to give a pair between the neutral aminonitropyridone and the corresponding deprotonated anion, a deprotonated Z pyridone 25 . In these crystals, the negative charges are compensated by either ammonium or sodium cations, which coordinate the nitro groups.…”

Section: Introductionmentioning

confidence: 99%

A New Folding Motif Formed with an Expanded Genetic Alphabet

Benner

Wang

Rocca

et al. 2022

Preprint

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Adding nucleotide pairs to a DNA alphabet not only increases the linear information density of DNA molecules, but also may increase the diversity of folds available to the molecular system. Reported here is an example of this. A single additional nucleotide, with the 5-nitro-6-aminopyridone ("Z") heterocycle, selected from an artificially expanded genetic information system (AEGIS), was incorporated at twelve sites into a DNA strand 23 nucleotides in length. With a fluor at its 5'-end and a quencher at its 3'-end, this molecule is shown by fluorescence quenching to fold in mildly alkaline (pH 8-9) conditions. This folded structure is quite stable, melting at Tm = 66.5 ℃ at pH 8.5. Spectroscopic, gel, and 2-dimensional NMR (800 MHz) analyses show that the structure is held together by "reverse" Z-:Z base pairs, which have been previously seen in a crystal structure of the free heterocycle, 5-nitro-6-aminopyridone. This, in turn, requires that the strands joined by Z-:Z reverse pairs be oriented in parallel. This, in turn, requires the fold to have a four stranded compact "down-up-down-up" fold. The structure does not form when various Zs are replaced or scrambled. Of two possible structures, we also considered the possibility of "intercalated" Z-:Z base pairs, a fold that resemble the i-motif of standard DNA where an analogous "down-up-down-up" fold is held together by C:C+ pairing at lower pH between parallel strands. An alternative model has a "down-up-down-up" fold without intercalation.

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“…These observations drive our interest in the detailed structure of the individual Z and P heterocycles, in part since detailed analysis of the structural properties of the heterocycles themselves might help in the design of polymerases that exclude these charged mismatches. A structure of the nucleobase Z, which unexpectedly cocrystallized as a mixture of its protonated and deprotonated forms in a Z-only crystal (Matsuura et al, 2016), has already served this role. We considered it might be possible that P also crystallizes as a mixture of P and P + in a P-only crystal.…”

Section: Introductionmentioning

confidence: 99%

The surprising pairing of 2-aminoimidazo[1,2-a][1,3,5]triazin-4-one, a component of an expanded DNA alphabet

2019

Self Cite

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Supporting information: this article has supporting information at journals.iucr.org/cThe surprising pairing of 2-aminoimidazo[1,2-a]- [1,3,5]triazin-4-one, a component of an expandedSynthetic biologists demonstrate their command over natural biology by reproducing the behaviors of natural living systems on synthetic biomolecular platforms. For nucleic acids, this is being done stepwise, first by adding replicable nucleotides to DNA, and then removing its standard nucleotides. This challenge has been met in vitro with 'six-letter' DNA and RNA, where the Watson-Crick pairing 'concept' is recruited to increase the number of independently replicable nucleotides from four to six. The two nucleobases most successfully added so far are Z and P, which present a donor-donor-acceptor and an acceptor-acceptordonor pattern, respectively. This pair of nucleobases are part of an 'artificially expanded genetic information system' (AEGIS). The Z nucleobase has been already crystallized, characterized, and published in this journal . Acta Cryst. C72, 952-959]. More recently, variants of Taq polymerase have been crystallized with the pair P:Z trapped in the active site. Here we report the crystal structure of the nucleobase 2-aminoimidazo[1,2-a][1,3,5]triazin-4-one (trivially named P) as the monohydrate, C 5 H 5 N 5 OÁH 2 O. The nucleobase P was crystallized from water and characterized by X-ray diffraction. Interestingly, the crystal structure shows two tautomers of P packed in a Watson-Crick fashion that cocrystallized in a 1:1 ratio. research papers 28 Laos et al. A component of an expanded DNA alphabet Acta Cryst. (2019). C75, 22-28 supporting information sup-1 Acta Cryst. (2019). C75, 22-28 supporting information Acta Cryst. (2019). C75, 22-28 [https://doi.

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Crystal structures of deprotonated nucleobases from an expanded DNA alphabet

Cited by 5 publications

References 52 publications

Multifacial Recognition in Binary and Ternary Cocrystals from 5-Halouracil and Aminoazine Derivatives

Multifacial Recognition in Binary and Ternary Cocrystals from 5-Halouracil and Aminoazine Derivatives

A New Folding Motif Formed with an Expanded Genetic Alphabet

The surprising pairing of 2-aminoimidazo[1,2-a][1,3,5]triazin-4-one, a component of an expanded DNA alphabet

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