Chemical Amplification through Template-Directed Synthesis

Zhan, Zheng-Yun J.; Lynn, David G.

doi:10.1021/ja972870v

Cited by 121 publications

(92 citation statements)

References 11 publications

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“…Many researchers have approached these problems by focusing on chemical modification of the modern nucleic acid structure. redIn one approach, template or fragment strands are chemically modified at specific sites so that once ligation occurs, the resulting template-copy duplex is destabilized, resulting in enhanced turnover numbers [120][121][122]. However, it is debatable whether the proposed alternative backbones or base replacements are prebiotically plausible.…”

Section: Selectionmentioning

confidence: 99%

A Chemical Engineering Perspective on the Origins of Life

Grover

Hsieh

et al. 2015

Processes

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Atoms and molecules assemble into materials, with the material structure determining the properties and ultimate function. Human-made materials and systems have achieved great complexity, such as the integrated circuit and the modern airplane. However, they still do not rival the adaptivity and robustness of biological systems. Understanding the reaction and assembly of molecules on the early Earth is a scientific grand challenge, and also can elucidate the design principles underlying biological materials and systems. This research requires understanding of chemical reactions, thermodynamics, fluid mechanics, heat and mass transfer, optimization, and control. Thus, the discipline of chemical engineering can play a central role in advancing the field. In this paper, an overview of research in the origins field is given, with particular emphasis on the origin of biopolymers and the role of chemical engineering phenomena. A case study is presented to highlight the importance of the environment and its coupling to the chemistry.

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Section: Selectionmentioning

confidence: 99%

A Chemical Engineering Perspective on the Origins of Life

Grover

Hsieh

et al. 2015

Processes

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“…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)(2)(3)(4)(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)(7)(8)(9).…”

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confidence: 99%

A self-replicating ligase ribozyme

Paul

Joyce²

2002

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

233

161

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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 equilibrium constants in Figure 9, K 1-4 , originally estimated, 63 were determined directly from 1 H-and 15 N-nmr experiments. 71 The relative concentration of the duplex to the free imine single strand, expressed as a function of K 2 /K 4 , was Ն10…”

Section: Figurementioning

confidence: 99%