Peptide Ligation and RNA Cleavage via an Abiotic Template Interface

Piao, Xijun; Xia, Xin; Mao, Jie; Bong, Dennis

doi:10.1021/jacs.5b00236

Cited by 22 publications

(28 citation statements)

References 59 publications

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“…[172,173] Interestingly, a construct equipped with tris(2-aminoethyl)amine [170] was reported to target and trigger hydrolytic nucleic acid cleavage via a general base mechanism. [174] Bong and coworkers have also used melamine as a synthetic base to bind to oligo T/U internal bulge sites, by macromolecular display of the triazine on sidechains of α-peptides [175][176][177][178][179][180] and other scaffolds, [181][182][183][184][185] yielding a family of compounds collectively called bifacial peptide nucleic acids (bPNAs) (Figure 8). Multivalent display of melamine in polymers and lipids [186][187][188] was found to encapsulate 5-fluorouracil and direct assembly and vesicle fusion with complementary hydrogen-bonding lipids and peptides directed by complementary hydrogen-bonding; [164] likewise, oligo-A DNA was found to assemble around free cyanuric acid [189] and oligo-T DNA can assemble around free melamine.…”

Section: Targeting Tt/uu Mismatchesmentioning

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: Targeting Tt/uu Mismatchesmentioning

confidence: 99%

Unnatural bases for recognition of noncoding nucleic acid interfaces

et al. 2020

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“…5 We report herein design and synthesis of small molecule tren derivatives that trigger the global folding of unstructured nucleic acid; further, these motifs mediate tertiary interactions between oligo-U domains in partially folded RNA. Binding is brokered by the same melamine base previously reported in bPNA, a family of peptoid, 6 peptide, 7–11 and polyacrylates 12,13 that triplex hybridize with DNA/RNA via base tripling triazine recognition 14–18 with thymine/uracil. In contrast to artificial base pairs, 19–22 there are fewer examples of artificial base triples, 23 despite considerable interest in triplex structures.…”

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confidence: 73%

Small Molecule Recognition Triggers Secondary and Tertiary Interactions in DNA Folding and Hammerhead Ribozyme Catalysis

2017

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We have identified tris(2-aminoethyl)amine (tren)-derived scaffolds with two (t2M) or four (t4M) melamine rings that can target oligo T/U domains in DNA/RNA. Unstructured T-rich DNAs cooperatively fold with the tren derivatives to form hairpin-like structures. Both t2M and t4M act as functional switches in a family of hammerhead ribozymes deactivated by stem or loop replacement with a U-rich sequence. Catalysis of bond scission in these hammerhead ribozymes could be restored by putative t2M/t4M refolding of stem secondary structure or tertiary bridging interactions between loop and stem. The simplicity of the t2M/t4M binding site enables programming of allostery in RNAs, recoding oligo-U domains as potential sites for secondary structure or tertiary contact. In combination with a facile and general method for installation of the t2M motif on primary amines, the method described herein streamlines design of synthetic allosteric riboswitches and small molecule−nucleic acid complexes.

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“…These bPNA hybrid stems can structurally replace native duplexes, allowing allosteric regulation of aptamer and ribozyme function. 85 − 87 The triplex hybridization is functional with different backbones: peptides, 88 , 89 peptoids, 90 and polyacrylates. 85 Bifacial polyacrylate nucleic acid (bP o NA), produced by functionalizing polyacrylate backbones with melamine bases, hybridize with DNA/RNA to load polymer nanoparticles and display targeting modalities on siRNA duplexes.…”

Section: Rna Chemical Modifications: Implications For Serum Stabilitymentioning

confidence: 99%

“…Using this method, a bP o NA and cholesterol-modified siRNA duplex targeting firefly luciferase was delivered into HeLa-Luc cells (expressing both firefly and renilla luciferase) to yield up to 40% luciferase silencing. 85 − 87 …”

Section: Rna Chemical Modifications: Implications For Serum Stabilitymentioning

confidence: 99%

Advancement of the Emerging Field of RNA Nanotechnology

Jasinski¹,

Haque²,

et al. 2017

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The field of RNA nanotechnology has advanced rapidly during the past decade. A variety of programmable RNA nanoparticles with defined shape, size, and stoichiometry have been developed for diverse applications in nanobiotechnology. The rising popularity of RNA nanoparticles is due to a number of factors: (1) removing the concern of RNA degradation in vitro and in vivo by introducing chemical modification into nucleotides without significant alteration of the RNA property in folding and self-assembly; (2) confirming the concept that RNA displays very high thermodynamic stability and is suitable for in vivo trafficking and other applications; (3) obtaining the knowledge to tune the immunogenic properties of synthetic RNA constructs for in vivo applications; (4) increased understanding of the 4D structure and intermolecular interaction of RNA molecules; (5) developing methods to control shape, size, and stoichiometry of RNA nanoparticles; (6) increasing knowledge of regulation and processing functions of RNA in cells; (7) decreasing cost of RNA production by biological and chemical synthesis; and (8) proving the concept that RNA is a safe and specific therapeutic modality for cancer and other diseases with little or no accumulation in vital organs. Other applications of RNA nanotechnology, such as adapting them to construct 2D, 3D, and 4D structures for use in tissue engineering, biosensing, resistive biomemory, and potential computer logic gate modules, have stimulated the interest of the scientific community. This review aims to outline the current state of the art of RNA nanoparticles as programmable smart complexes and offers perspectives on the promising avenues of research in this fast-growing field.

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Peptide Ligation and RNA Cleavage via an Abiotic Template Interface

Cited by 22 publications

References 59 publications

Unnatural bases for recognition of noncoding nucleic acid interfaces

Unnatural bases for recognition of noncoding nucleic acid interfaces

Small Molecule Recognition Triggers Secondary and Tertiary Interactions in DNA Folding and Hammerhead Ribozyme Catalysis

Advancement of the Emerging Field of RNA Nanotechnology

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