Synthesis of Janus Compounds for the Recognition of G-U Mismatched Nucleobase Pairs

Artigas, Gerard; Marchán, Vicente

doi:10.1021/jo401684j

Cited by 18 publications

(20 citation statements)

References 54 publications

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“…Artigas and Marchan reported the synthesis of two bicyclic systems designed to insert between GU in RNA hairpins when coupled to the aminoglycoside neamine core, which has inherent groove binding function. [ 161 ] Though increased RNA binding was observed by introducing GU pairs, it remained difficult to separate the contributions of multiple factors to changes in binding.…”

Section: Unnatural Bases In Noncanonical Interactionsmentioning

confidence: 99%

Unnatural bases for recognition of noncoding nucleic acid interfaces

et al. 2020

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The notion of using synthetic heterocycles instead of the native bases to interface with DNA and RNA has been explored for nearly 60 years. Unnatural bases compatible with the DNA/RNA coding interface have the potential to expand the genetic code and co‐opt the machinery of biology to access new macromolecular function; accordingly, this body of research is core to synthetic biology. While much of the literature on artificial bases focuses on code expansion, there is a significant and growing effort on docking synthetic heterocycles to noncoding nucleic acid interfaces; this approach seeks to illuminate major processes of nucleic acids, including regulation of transcription, translation, transport, and transcript lifetimes. These major avenues of research at the coding and noncoding interfaces have in common fundamental principles in molecular recognition. Herein, we provide an overview of foundational literature in biophysics of base recognition and unnatural bases in coding to provide context for the developing area of targeting noncoding nucleic acid interfaces with synthetic bases, with a focus on systems developed through iterative design and biophysical study.

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Section: Unnatural Bases In Noncanonical Interactionsmentioning

confidence: 99%

Unnatural bases for recognition of noncoding nucleic acid interfaces

et al. 2020

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“…This result gives important insight in the potential for recognition of mismatched nucleobase pairs as versatile tool in the emerging area of synthetic biology. [88][89][90][91][92] 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 12…”

Section: Methodsmentioning

confidence: 99%

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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“…The concept of bifacial nucleic acid recognition, however, is not new. It was conceived by Lehn 30 more than two decades ago and, subsequently, expounded upon by others in the development of Januswedges [31][32][33][34][35][36][37][38] . Despite concerted efforts from several research groups, only a small set of Janus-wedges has been developed, and they vary considerably in shapes and sizes, such that they cannot be effectively combined in a modular format for recognition of a non-homogenous nucleic acid sequence.…”

Section: Resultsmentioning

confidence: 99%

Shape selective bifacial recognition of double helical DNA

et al. 2018

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An impressive array of antigene approaches has been developed for recognition of double helical DNA over the past three decades; however, few have exploited the 'Watson-Crick' base-pairing rules for establishing sequence-specific recognition. One approach employs peptide nucleic acid as a molecular reagent and strand invasion as a binding mode. However, even with integration of the latest conformationally-preorganized backbone design, such an approach is generally confined to sub-physiological conditions due to the lack of binding energy. Here we report the use of a class of shape-selective, bifacial nucleic acid recognition elements, namely Janus bases, for targeting double helical DNA or RNA. Binding occurs in a highly sequence-specific manner under physiologically relevant conditions. The work may provide a foundation for the design of oligonucleotides for targeting the secondary and tertiary structures of nucleic acid biopolymers.

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Synthesis of Janus Compounds for the Recognition of G-U Mismatched Nucleobase Pairs

Cited by 18 publications

References 54 publications

Unnatural bases for recognition of noncoding nucleic acid interfaces

Unnatural bases for recognition of noncoding nucleic acid interfaces

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

Shape selective bifacial recognition of double helical DNA

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