Replicating DNA Differently

Zhan, Zheng-Yun J.; Ye, Jing‐Dong; Li, Xiaoyu; Lynn, David G.

doi:10.2174/1385272013375085

Cited by 19 publications

(21 citation statements)

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“…[1,14,[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] More recently, researchers have discovered the ability of DNA-templated organic synthesis to direct the creation of structures unrelated to the nucleic acid backbone. Introduction 4849 plated synthesis to nonbiological reactants used DNA or RNA hybridization to accelerate the formation of phosphodiester bonds or other structural mimics of the nucleic acid backbone.…”

Section: Introductionmentioning

confidence: 99%

DNA‐Templated Organic Synthesis: Nature's Strategy for Controlling Chemical Reactivity Applied to Synthetic Molecules

2004

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In contrast to the approach commonly taken by chemists, nature controls chemical reactivity by modulating the effective molarity of highly dilute reactants through macromolecule-templated synthesis. Nature's approach enables complex mixtures in a single solution to react with efficiencies and selectivities that cannot be achieved in conventional laboratory synthesis. DNA-templated organic synthesis (DTS) is emerging as a surprisingly general way to control the reactivity of synthetic molecules by using nature's effective-molarity-based approach. Recent developments have expanded the scope and capabilities of DTS from its origins as a model of prebiotic nucleic acid replication to its current ability to translate DNA sequences into complex small-molecule and polymer products of multistep organic synthesis. An understanding of fundamental principles underlying DTS has played an important role in these developments. Early applications of DTS include nucleic acid sensing, small-molecule discovery, and reaction discovery with the help of translation, selection, and amplification methods previously available only to biological molecules.

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Section: Introductionmentioning

confidence: 99%

DNA‐Templated Organic Synthesis: Nature's Strategy for Controlling Chemical Reactivity Applied to Synthetic Molecules

2004

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“…One or more of these products might direct the synthesis of the starting template. Cross-catalytic systems of this type have been demonstrated for nucleic acids, peptides, and small organic molecules (13,26,(28)(29)(30)(31)(32)(33)(34).…”

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confidence: 99%

A self-replicating ligase ribozyme

Paul

Joyce²

2002

Proc. Natl. Acad. Sci. U.S.A.

222

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A self-replicating molecule directs the covalent assembly of component molecules to form a product that is of identical composition to the parent. When the newly formed product also is able to direct the assembly of product molecules, the self-replicating system can be termed autocatalytic. A self-replicating system was developed based on a ribozyme that catalyzes the assembly of additional copies of itself through an RNA-catalyzed RNA ligation reaction. The R3C ligase ribozyme was redesigned so that it would ligate two substrates to generate an exact copy of itself, which then would behave in a similar manner. This self-replicating system depends on the catalytic nature of the RNA for the generation of copies. A linear dependence was observed between the initial rate of formation of new copies and the starting concentration of ribozyme, consistent with exponential growth. The autocatalytic rate constant was 0.011 min ؊1 , whereas the initial rate of reaction in the absence of pre-existing ribozyme was only 3.3 ؋ 10 ؊11 M⅐min ؊1 . Exponential growth was limited, however, because newly formed ribozyme molecules had greater difficulty forming a productive complex with the two substrates. Further optimization of the system may lead to the sustained exponential growth of ribozymes that undergo self-replication. In living systems, replicative processes transfer genetic information from template nucleic acid molecules to newly synthesized, complementary products. Several nonenzymatic templatedependent ligation systems have been devised to study the role of a template in binding and positioning complementary substrates for covalent bond formation (1-5). These have included simple self-replicating systems of the form A ϩ B 3 T, where A and B are substrates that bind to a complementary template, T, and become joined to form a product molecule that is identical to the template (6-9). The unique aspect of self-replicating systems is that the reaction product has the potential to direct additional reactions. The system is termed autocatalytic when the product is an efficient template, and each covalent bond that is formed generates additional template molecules that can direct further joining reactions. The realization of autocatalytic behavior in a self-replicating system implies that sustained exponential growth may be possible.The self-replicating systems that have been studied to date use template molecules composed of nucleic acids (6, 7, 10), peptides (11-14), or small organic compounds (15-17). The nucleic acid-based systems are the most straightforward and rely on simple Watson-Crick pairing interactions between a short oligonucleotide template and two complementary oligonucleotide substrates (6, 7, 10). The substrates are bound at adjacent positions along the template and are joined through a reaction involving chemical groups at their opposed ends. Peptide-based self-replicating systems are similar, except that the components are oligopeptides that have the capacity to form ␣-helices. The template is the hydrophob...

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“…The experimental work reported by Zhan et al 18 showed that adding a single amine bond can create a 10 6 -fold difference in K eq , resulting in the value of ΔG 25,amine = 8.75 kcal mol -1 . Such significant energy differences suggest that great control can be exerted over the reaction and that even longer sequences, approaching the complexity of simple ribozymes, might be used as catalytic templates.…”

Section: U N C O R R E C T E D P R O O Fmentioning

confidence: 99%

“…We have modeled the association of the rigid imine oligomer as equivalent to a DNA oligomer with the same nucleotide sequence. 18 To emulate the weaker association when an amine bond is present, 18 an additional Gibbs energy penalty, ΔG 25,amine , is included for each amine bond as illustrated in Figure 2. The equilibrium constant for an oligomer with amine bonds is estimated using the thermodynamic parameters in Table 2, along with the additional ΔG 25,amine parameter for each amine bond present in the oligomer backbone.…”

Section: Modeling Template-directed Polymerization Reactionsmentioning

confidence: 99%