An Alternative Nucleobase Code: Characterization of Purine–Purine DNA Double Helices Bearing Guanine–Isoguanine and Diaminopurine 7‐Deaza‐Xanthine Base Pairs

Heuberger, Benjamin D.; Switzer, Christopher

doi:10.1002/cbic.200800450

Cited by 41 publications

(75 citation statements)

References 76 publications

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“…With regard to mononucleotide polymerization, it appears that the poor stacking of the pyrimidine nucleotides precludes assembly of mononucleotides by intercalating molecular midwives. The poor stacking of pyrimidine bases has prompted our laboratory, and several others (54)(55)(56), to reconsider an early proposal by Crick that the first RNA-like polymers might have used purine-purine base pairs (57). Our demonstration in the present work that intercalators can promote the polymerization of homo-adenine oligonucleotides represents the first step towards the realization of intercalation-mediated mononucleotide polymerization in a homo-purine system.…”

Section: Discussionmentioning

confidence: 65%

Intercalation as a means to suppress cyclization and promote polymerization of base-pairing oligonucleotides in a prebiotic world

Horowitz

Engelhart

Chen

et al. 2010

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

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The RNA world hypothesis proposes that nucleic acids were once responsible for both information storage and chemical catalysis, before the advent of coded protein synthesis. However, it is difficult to imagine how nucleic acid polymers first appeared, as the abiotic chemical formation of long nucleic acid polymers from mononucleotides or short oligonucleotides remains elusive, and barriers to achieving this goal are substantial. One specific obstacle to abiotic nucleic acid polymerization is strand cyclization. Chemically activated short oligonucleotides cyclize efficiently, which severely impairs polymer growth. We show that intercalation, which stabilizes and rigidifies nucleic acid duplexes, almost totally eliminates strand cyclization, allowing for chemical ligation of tetranucleotides into duplex polymers of up to 100 base pairs in length. In contrast, when these reactions are performed in the absence of intercalators, almost exclusively cyclic tetra-and octanucleotides are produced. Intercalator-free polymerization is not observed, even at tetranucleotide concentrations >10; 000-fold greater than those at which intercalators enable polymerization. We also demonstrate that intercalation-mediated polymerization is most favored if the size of the intercalator matches that of the base pair; intercalators that bind to Watson-Crick base pairs promote the polymerization of oligonucleotides that form these base pairs. Additionally, we demonstrate that intercalationmediated polymerization is possible with an alternative, nonWatson-Crick-paired duplex that selectively binds a complementary intercalator. These results support the hypothesis that intercalators (acting as 'molecular midwives') could have facilitated the polymerization of the first nucleic acids and possibly helped select the first base pairs, even if only trace amounts of suitable oligomers were available.base pair selection | origin of life | RNA world | polymerization | molecular evolution O ver the past two decades, significant evidence has been presented in support of the RNA world hypothesis, which proposes that RNA polymers predated coded proteins in early life (1, 2). Current support for this hypothesis includes the fact that contemporary life still uses RNA as an informational polymer and in chemical catalysis (3). The ability of RNA to catalyze reactions is exemplified by natural and artificial ribozymes that promote a wide variety of chemical reactions (4) as well as the observation that the catalytic core of the ribosome is comprised of RNA (5). Despite the attractiveness of the RNA world as a hypothetical stage of early life, it remains unclear how RNA [or a predecessor of RNA (6-11)] would initially have been synthesized without the aid of protein enzyme catalysis.Several distinct proposals have been presented for the abiotic origin of the first RNA polymers (10,(12)(13)(14)(15)(16)(17). Perhaps the most notable is that of Ferris and coworkers, in which mineral surfaces are used to locally concentrate and promote the polymerization of liga...

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Section: Discussionmentioning

confidence: 65%

Intercalation as a means to suppress cyclization and promote polymerization of base-pairing oligonucleotides in a prebiotic world

Horowitz

Engelhart

Chen

et al. 2010

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

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“…[98][99][100][101] Von diesen Eigenschaften sind die wichtigsten: In der homo-DNA sind alle vier kanonischen Watson-CrickPaarungen stärker als in der DNA; homobasische Sequenzen von Adenin zeigen starke Adenin-Adenin-Paarung im reverse-Hoogsteen-Modus, ebenso verhalten sich homobasische Sequenzen von Guanin (Abbildung 27); beide PurinPurin-Paare sind stärker als das kanonische Adenin-ThyminPaar, das Guanin-Guanin-Paar jedoch schwächer als das kanonische Guanin-Cytosin-Paar. Hieraus resultiert -abhängig von der Basensequenz -eine zu DNA unterschiedliche Paa- [103,104] zu seiner Synthese der "Bicyclo-DNA" gezielt eingesetzt.…”

Section: Angewandte Chemieunclassified

Ätiologie potentiell primordialer Biomolekül‐Strukturen: Vom Vitamin B₁₂zu den Nukleinsäuren und der Frage nach der Chemie der Entstehung des Lebens – ein Rückblick

Eschenmoser

2011

Angewandte Chemie

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“Wir werden es nie wissen können” ist ein Truismus, der zu Resignation gegenüber jeglicher experimenteller Investition in eine Suche nach der Chemie der Entstehung des Lebens verführt. Doch widerspricht solche Resignation radikal der Herausforderung, die der Chemie als Naturwissenschaft auferlegt ist. Ungeachtet der Prognose, wonach der kürzeste Weg zum Verständnis der Metamorphose des Chemischen ins Biologische über die experimentelle Modellierung “künstlichen chemischen Lebens” führt, wird die naturwissenschaftliche Suche nach dem von der Natur begangenen Weg der Entstehung des Lebens, das wir kennen, wohl nie wirklich enden. Denn sie ist Teil der Suche nach unserem eigenen Ursprung.

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“…Problems were also encountered with self association of certain sequences, which is not unexpected when dealing with purine-rich systems. [37] An unnatural, pyrimidine-only system has been explored by Inouye et al in which all four native bases were replaced with pyrimidine-alkynyl analogues iG* (23), iC* (24), A* (25) and T* (26). Numerous oligonucleotides incorporating these modified bases have been explored and overall the duplexes that were formed were similar in stability to native duplexes.…”

Section: Nucleobase Modificationsmentioning

confidence: 99%

Chemical Modification of Oligonucleotides for Therapeutic, Bioanalytical and other Applications

2009

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Although known for more than a century, bromine trifluoride is not a common reagent in day to day research work in organic chemistry. Its tendency to react exothermically with solvents containing Lewis base elements such as water, acetone or ethers distanced it from the mind of many. Still, under the proper conditions, it can perform quite a few selective reactions which are difficult to achieve by other reagents. We discuss in this review reactions which have been published in the last 30 years. They consist of fluorinating heteroatoms, substituting carbon‐halogen bonds with carbon‐fluorine bonds, syntheses of anesthetics, construction of the trifluoromethyl (CF3) and the difluoromethylene (CF2) groups, aromatic brominations and more.

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An Alternative Nucleobase Code: Characterization of Purine–Purine DNA Double Helices Bearing Guanine–Isoguanine and Diaminopurine 7‐Deaza‐Xanthine Base Pairs

Cited by 41 publications

References 76 publications

Intercalation as a means to suppress cyclization and promote polymerization of base-pairing oligonucleotides in a prebiotic world

Intercalation as a means to suppress cyclization and promote polymerization of base-pairing oligonucleotides in a prebiotic world

Ätiologie potentiell primordialer Biomolekül‐Strukturen: Vom Vitamin B₁₂zu den Nukleinsäuren und der Frage nach der Chemie der Entstehung des Lebens – ein Rückblick

Chemical Modification of Oligonucleotides for Therapeutic, Bioanalytical and other Applications

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An Alternative Nucleobase Code: Characterization of Purine–Purine DNA Double Helices Bearing Guanine–Isoguanine and Diaminopurine 7‐Deaza‐Xanthine Base Pairs

Cited by 41 publications

References 76 publications

Intercalation as a means to suppress cyclization and promote polymerization of base-pairing oligonucleotides in a prebiotic world

Intercalation as a means to suppress cyclization and promote polymerization of base-pairing oligonucleotides in a prebiotic world

Ätiologie potentiell primordialer Biomolekül‐Strukturen: Vom Vitamin B12zu den Nukleinsäuren und der Frage nach der Chemie der Entstehung des Lebens – ein Rückblick

Chemical Modification of Oligonucleotides for Therapeutic, Bioanalytical and other Applications

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Product

Resources

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Ätiologie potentiell primordialer Biomolekül‐Strukturen: Vom Vitamin B₁₂zu den Nukleinsäuren und der Frage nach der Chemie der Entstehung des Lebens – ein Rückblick