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Jurinovic, K.

Publications and source records attributed to Jurinovic, K..

2 recordsLinked to original sources

Far-from-equilibrium assembly of multimers through DNA-based catalytic templating

On-demand assembly of arbitrary, sequence-defined polymers from a pool of monomers is a major challenge in modern chemistry, towards which limited progress has been made. By contrast, biological systems routinely use information-bearing DNA and RNA templates to catalytically synthesize a precise, far-from-equilibrium ensemble of nucleic acid and protein sequences from the available pools of nucleoside triphosphates or aminoacyl-tRNAs. Inspired by these biological examples, we introduce an enzyme-free DNA strand displacement network in which single-stranded DNA sequences template the assembly of specific non-covalent DNA multimers of up to length five, under isothermal and autonomous conditions. The templates overcome product inhibition and can thereby catalyse the formation of a far-from-equilibrium ensemble of long-lived metastable products that are not otherwise addressable.

biophysics↗

Fuel-driven catalytic molecular templating

Catalytic molecular templating, wherein a copolymer molecule serves as a sequence-specific template to propagate genetic information to a daughter copolymer, is fundamental to cells. Templating underlies DNA replication, RNA transcription and protein translation, underpinning the molecular basis of heredity, evolution, and biological function, and allowing staggering complexity to arise from simple building blocks. It has hitherto been challenging to emulate templating without highly evolved enzymes, largely due to product inhibition of catalytic turnover, which is a major challenge for templated dimerization and prohibitive for longer products. We present an enzyme-free DNA-based templated dimerization reaction enabled and controlled by a fuel strand that actively displaces the product from the template only once dimerization is complete, overcoming product inhibition. We systematically investigate design variants to optimise catalytic turnover, and demonstrate information propagation through the action of distinct templates that assemble specific products from the same pool of building blocks. We also show that the fuel represents an input by which the templating can be controlled, allowing the coupling of catalytic turnover to the output of upstream DNA circuitry. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/706517v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@e82eeeorg.highwire.dtl.DTLVardef@1612b85org.highwire.dtl.DTLVardef@706911org.highwire.dtl.DTLVardef@217d6_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗