Efficient Self-Assembly in Water of Long Noncovalent Polymers by Nucleobase Analogues

Cafferty, Brian J.; Gállego, Isaac; Chen, Michael C.; Farley, Katherine I.; Eritja, Ramón; Hud, Nicholas V.

doi:10.1021/ja312155v

Cited by 156 publications

(171 citation statements)

References 30 publications

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“…It is essential to address this significant gap in knowledge, since these interactions could collectively affect the outcome (e.g., polymer yields, sequence space, and length) of RNA polymerization, particularly in prebiotic environments that lack the biological tools responsible for regulation of RNA polymerization in modern biology. This line of inquiry complements recent explorations by others on molecular self-assembly in prebiotic environments (Deamer et al, 2006), nucleotide aggregation (e.g., Raszka and Kaplan, 1972;Rymden and Stilbs, 1985;Eimer and Dorfmuller, 1992), and self-assembly of nucleobase analogues (Cafferty et al, 2013).…”

Section: Introductionsupporting

confidence: 65%

Guanine-Centric Self-Assembly of Nucleotides in Water: An Important Consideration in Prebiotic Chemistry

Cassidy

Burcar²,

Stevens³

et al. 2014

Astrobiology

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Investigations of plausible prebiotic chemistry on early Earth must consider not only chemical reactions to form more complex products such as proto-biopolymers but also reversible, molecular self-assembly that would influence the availability, organization, and sequestration of reactant molecules. The self-assembly of guanosine compounds into higher-order structures and lyotropic liquid crystalline ''gel'' phases through formation of hydrogen-bonded guanine tetrads (G-tetrads) is one such consideration that is particularly relevant to an RNAworld scenario. G-tetrad-based gelation has been well studied for individual guanosine compounds and was recently observed in mixtures of guanosine with 5¢-guanosine monophosphate (GMP) as well. The present work investigates the self-assembly of GMP in the presence of the other RNA nucleotides. Effects of the total concentration and relative proportion of the nucleotides in the mixtures, the form (disodium salt vs. free acid) of the nucleotides, temperature, pH, and salt concentration were determined by visual observations and circular dichroism (CD) spectroscopy. The results show that formation of cholesteric G-tetrad phases is influenced by interactions with other nucleotides, likely through association (e.g., intercalation) of the nucleotides with the Gtetrad structures. These interactions affect the structure and stability of the G-tetrad gel phase, as well as the formation of alternate self-assembled GMP structures such as a continuous, hydrogen-bonded GMP helix or dimers and aggregates of GMP. These interactions and multiple equilibria are influenced by the presence of cations, especially in the presence of K + . This work could have important implications for the emergence of an RNA or proto-RNA world, which would require mixtures of nucleotides at sufficiently high, local concentrations for abiotic polymerization to occur.

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Section: Introductionsupporting

confidence: 65%

Guanine-Centric Self-Assembly of Nucleotides in Water: An Important Consideration in Prebiotic Chemistry

Cassidy

Burcar²,

Stevens³

et al. 2014

Astrobiology

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“…Further, base analogs modified for enhanced stacking form paired, free stacks thousands of residues in length (Cafferty et al 2013). A completely paired template-nucleotide complex like the calculated one (Fig.…”

Section: Runaway Stacksmentioning

confidence: 65%

Cross-backbone templating; ribodinucleotides made on poly(C)

Majerfeld

Puthenvedu

Yarus

2016

RNA

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′ G synthesis from pG and chemically activated 2MeImpG is accelerated by the addition of complementary poly(C), but affected only slightly by poly(G) and not at all by poly(U) and poly(A). This suggests that 3 ′ -5 ′ poly(C) is a template for uncatalyzed synthesis of 5 ′ -5 ′ GppG, as was poly(U) for AppA synthesis, previously. The reaction occurs at 50 mM monoand divalent ion concentrations, at moderate temperatures, and near pH 7. The reactive complex at the site of enhanced synthesis of 5 ′ -5 ′ GppG seems to contain a single pG, a single phosphate-activated nucleotide 2MeImpG, and a single strand of poly(C). Most likely this structure is base-paired, as the poly(C)-enhanced reaction is completely disrupted between 30 and 37°C, whereas slower, untemplated synthesis of GppG accelerates. More specifically, the reactive center acts as would be expected for short, isolated G nucleotide stacks expanded and ordered by added poly(C). For example, poly(C)-mediated GppG production is very nonlinear in overall nucleotide concentration. Uncatalyzed NppN synthesis is now known for two polymers and their complementary free nucleotides. These data suggest that varied, simple, primordial 3 ′ -5 ′ RNA sequences could express a specific chemical phenotype by encoding synthesis of complementary, reactive, coenzyme-like 5 ′ -5 ′ ribodinucleotides.

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“…Hud et al have demonstrated self--assembly of CA with hydrophilic derivatives of 2,4,6--triaminopyrimidine (TAP) in water, including a monomeric TAP--ribose derivative 46 . These mixtures produced hexameric rosettes that stacked into long fibers with a similar diameter to the d(A n ):CA structure described here.…”

Section: Investigation Of Fiber Structurementioning

confidence: 99%

Reprogramming the assembly of unmodified DNA with a small molecule

et al. 2016

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The information storage and encoding ability of DNA arise from a remarkably simple 4--letter -A, T, G, C nucleobase code. Expanding this DNA 'alphabet' provides information about its function and evolution, and introduces new functionalities into nucleic acids and organisms. Previous efforts relied on the synthetically demanding incorporation of non--canonical bases into nucleosides. Here we report the discovery that a small molecule, cyanuric acid, with three thymine--like faces reprograms the assembly of unmodified poly(adenine) into stable, long and abundant fibers with a unique internal structure. Poly(A) DNA, RNA and PNA all form these assemblies. Our studies are consistent with the association of adenine and cyanuric acid units into a hexameric rosette, bringing together poly(A) triplexes with subsequent cooperative polymerization. Fundamentally, this study shows that small hydrogen--bonding molecules can be used to induce the assembly of nucleic acids in water, leading to new structures from inexpensive and readily available materials.

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Efficient Self-Assembly in Water of Long Noncovalent Polymers by Nucleobase Analogues

Cited by 156 publications

References 30 publications

Guanine-Centric Self-Assembly of Nucleotides in Water: An Important Consideration in Prebiotic Chemistry

Guanine-Centric Self-Assembly of Nucleotides in Water: An Important Consideration in Prebiotic Chemistry

Cross-backbone templating; ribodinucleotides made on poly(C)

Reprogramming the assembly of unmodified DNA with a small molecule

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