Template-Triggered Emergence of a Self-Replicator from a Dynamic Combinatorial Library.

Self-assembly of a specific member of a dynamic combinatorial library (DCL) may lead to self-replication of this molecule. However, if the concentration of the potential replicator in the DCL fails to exceed its critical aggregation concentration (CAC), then self-replication will not occur. We now show how addition of a template can raise the concentration of a library member-template complex beyond its CAC, leading to the onset of self-replication. Once in existence, the replicator aggregates promote further replication also in the absence of the template that induced the initial emergence of the replicator.

[1]  B. Gibb.  Teetering towards chaos and complexity. , 2009, Nature chemistry.

[2]  Yixian Zheng,et al.  Nucleation of microtubule assembly by a γ-tubulin-containing ring complex , 1995, Nature.

[3]  Dominic J Campopiano,et al.  Bivalent enzyme inhibitors discovered using dynamic covalent chemistry. , 2012, Chemistry.

[4]  G. Salinas,et al.  Discovering Echinococcus granulosus thioredoxin glutathione reductase inhibitors through site-specific dynamic combinatorial chemistry , 2014, Molecular Diversity.

[5]  N. Wagner,et al.  Chemical and light triggering of peptide networks under partial thermodynamic control. , 2012, Chemical communications.

[6]  Jonathan R. Nitschke,et al.  Systems chemistry: Molecular networks come of age , 2009, Nature.

[7]  J. Sanders,et al.  Evolution of dynamic combinatorial chemistry. , 2012, Accounts of chemical research.

[8]  Nicholas K. Pinkin,et al.  Development and mechanistic studies of an optimized receptor for trimethyllysine using iterative redesign by dynamic combinatorial chemistry. , 2014, Organic & biomolecular chemistry.

[9]  N. Lehman.  What is Life? How Chemistry Becomes Biology , 2013 .

[10]  M. Nakamori,et al.  From dynamic combinatorial ‘hit’ to lead: in vitro and in vivo activity of compounds targeting the pathogenic RNAs that cause myotonic dystrophy , 2012, Nucleic acids research.

[11]  Piotr Nowak,et al.  Dynamic combinatorial libraries: from exploring molecular recognition to systems chemistry. , 2013, Journal of the American Chemical Society.

[12]  P. Herdewijn,et al.  Welcome Home, Systems Chemists! , 2010 .

[13]  Rein V Ulijn,et al.  Enzyme-assisted self-assembly under thermodynamic control. , 2009, Nature nanotechnology.

[14]  S. Otto,et al.  Solvent composition dictates emergence in dynamic molecular networks containing competing replicators. , 2015, Journal of the American Chemical Society.

[15]  Joost N. H. Reek,et al.  Dynamic Combinatorial Chemistry in Chemical Catalysis , 2013 .

[16]  Jean-Marie Lehn,et al.  From supramolecular chemistry towards constitutional dynamic chemistry and adaptive chemistry. , 2007, Chemical Society reviews.

[17]  S. Otto,et al.  Localized template-driven functionalization of nanoparticles by dynamic combinatorial chemistry. , 2015, Angewandte Chemie.

[18]  Michael L. Manapat,et al.  Spontaneous network formation among cooperative RNA replicators , 2012, Nature.

[19]  K. Ruiz-Mirazo,et al.  Prebiotic systems chemistry: new perspectives for the origins of life. , 2014, Chemical reviews.

[20]  N. Giuseppone,et al.  Self-duplicating amplification in a dynamic combinatorial library. , 2008, Journal of the American Chemical Society.

[21]  R. Ulijn,et al.  Discovery of energy transfer nanostructures using gelation-driven dynamic combinatorial libraries , 2013 .

[22]  Zehavit Dadon,et al.  Replication NAND gate with light as input and output. , 2011, Chemical communications.

[23]  Douglas Philp,et al.  Design and implementation of a highly selective minimal self-replicating system. , 2006, Angewandte Chemie.

[24]  S. Otto,et al.  Catenanes from catenanes: quantitative assessment of cooperativity in dynamic combinatorial catenation , 2014 .

[25]  J. Lehn.  Perspectives in chemistry--steps towards complex matter. , 2013, Angewandte Chemie.

[26]  Günter von Kiedrowski,et al.  Self replicating systems , 2007 .

[27]  Benjamin L Miller,et al.  Dynamic combinatorial selection of molecules capable of inhibiting the (CUG) repeat RNA-MBNL1 interaction in vitro: discovery of lead compounds targeting myotonic dystrophy (DM1). , 2008, Journal of the American Chemical Society.

[28]  Sijbren Otto,et al.  Hydrogel formation upon photoinduced covalent capture of macrocycle stacks from dynamic combinatorial libraries. , 2011, Angewandte Chemie.

[29]  Gerald F. Joyce,et al.  Ligand-dependent exponential amplification of a self-replicating L-RNA enzyme. , 2012, Journal of the American Chemical Society.

[30]  N. Giuseppone,et al.  Dynablocks: Structural Modulation of Responsive Combinatorial Self-Assemblies at Mesoscale , 2009 .

[31]  J. Sanders,et al.  Dynamic combinatorial libraries for the recognition of heavy metal ions. , 2012, Organic & biomolecular chemistry.

[32]  S. Otto,et al.  An allosteric receptor by simultaneous "casting" and "molding" in a dynamic combinatorial library. , 2015, Angewandte Chemie.

[33]  Nicolas Giuseppone,et al.  Dynamic combinatorial evolution within self-replicating supramolecular assemblies. , 2009, Angewandte Chemie.

[34]  Evan A. Wood,et al.  Designing instructable networks using synthetic replicators , 2010 .

[35]  Nicolas Giuseppone,et al.  Toward self-constructing materials: a systems chemistry approach. , 2012, Accounts of chemical research.

[36]  S. Otto,et al.  Uncovering the selection criteria for the emergence of multi-building-block replicators from dynamic combinatorial libraries. , 2013, Journal of the American Chemical Society.

[37]  Junmei Wang,et al.  Development and testing of a general amber force field , 2004, J. Comput. Chem..

[38]  D. Philp,et al.  Target-driven selection in a dynamic nitrone library. , 2008, Chemical communications.

[39]  B. Miller,et al.  Ternary resin-bound Dynamic Combinatorial Chemistry. , 2012, Chemical communications.

[40]  S. P. Fletcher,et al.  Physical autocatalysis driven by a bond-forming thiol–ene reaction , 2014, Nature Communications.

[41]  R. Cacciapaglia,et al.  Target-induced amplification in a dynamic library of macrocycles. A quantitative study , 2012 .

[42]  Christopher A Waudby,et al.  Mechanosensitive Self-Replication Driven by Self-Organization , 2010, Science.

[43]  Jeremy K. M. Sanders,et al.  Dynamic Combinatorial Libraries of Macrocyclic Disulfides in Water , 2000 .

[44]  Carsten Kutzner,et al.  GROMACS 4:  Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation. , 2008, Journal of chemical theory and computation.

[45]  Andreas Herrmann,et al.  Dynamic combinatorial/covalent chemistry: a tool to read, generate and modulate the bioactivity of compounds and compound mixtures. , 2014, Chemical Society reviews.

[46]  R. C. Lirag,et al.  Kinetically controlled phenomena in dynamic combinatorial libraries. , 2014, Chemical Society reviews.

[47]  S. Otto,et al.  A "dial-a-receptor" dynamic combinatorial library. , 2013, Angewandte Chemie.

[48]  A. Stefankiewicz,et al.  Template-directed synthesis of multi-component organic cages in water , 2012 .

[49]  S. P. Fletcher,et al.  Mechanisms of autocatalysis. , 2013, Angewandte Chemie.

[50]  N. Hădade,et al.  Selective host molecules obtained by dynamic adaptive chemistry. , 2014, Chemistry.

[51]  B. Miller.  Dynamic combinatorial chemistry : in drug discovery, bioorganic chemistry, and materials science , 2010 .

[52]  N. Giuseppone,et al.  Experimental and theoretical methods for the analyses of dynamic combinatorial libraries , 2014 .

[53]  S. Maiti,et al.  Dynamic combinatorial chemistry on a monolayer protected gold nanoparticle. , 2015, Chemical communications.

[54]  Michael A McDonough,et al.  Dynamic combinatorial chemistry employing boronic acids/boronate esters leads to potent oxygenase inhibitors. , 2012, Angewandte Chemie.

[55]  Juan R. Granja,et al.  A self-replicating peptide , 1996, Nature.

[56]  N. Ashkenasy,et al.  Transient fibril structures facilitating nonenzymatic self-replication. , 2012, ACS nano.

[57]  G. Whitesides,et al.  Complexity in chemistry. , 1999, Science.

[58]  M. Ghadiri,et al.  Design of a directed molecular network. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[59]  L. James,et al.  A synthetic receptor for asymmetric dimethyl arginine. , 2013, Journal of the American Chemical Society.

[60]  S. Otto,et al.  An "ingredients" approach to functional self-synthesizing materials: a metal-ion-selective, multi-responsive, self-assembled hydrogel. , 2014, Chemistry.

[61]  J. Rebek,et al.  Autocatalysis and organocatalysis with synthetic structures , 2009, Proceedings of the National Academy of Sciences.

[62]  D. Philp,et al.  Making Molecules Make Themselves – the Chemistry of Artificial Replicators , 2009 .

[63]  S. Balasubramanian,et al.  Targeting nucleic acid secondary structures with polyamides using an optimized dynamic combinatorial approach. , 2005, Angewandte Chemie.

[64]  D. Sherrington,et al.  Dynamic combinatorial discovery of a [2]-catenane and its guest-induced conversion into a molecular square host. , 2008, Journal of the American Chemical Society.

[65]  M. Maaloum,et al.  Supramolecular self-assembly and radical kinetics in conducting self-replicating nanowires. , 2014, ACS nano.

[66]  S. Otto,et al.  Estimating equilibrium constants for aggregation from the product distribution of a dynamic combinatorial library. , 2009, Organic Letters.

[67]  J. Sanders,et al.  Host-guest binding constants can be estimated directly from the product distributions of dynamic combinatorial libraries. , 2007, Angewandte Chemie.

[68]  Günter von Kiedrowski,et al.  A Self‐Replicating Hexadeoxynucleotide , 1986 .

[69]  Milon Mondal,et al.  Dynamic combinatorial chemistry: a tool to facilitate the identification of inhibitors for protein targets. , 2015, Chemical Society reviews.

[70]  D. Philp,et al.  A simple synthetic replicator amplifies itself from a dynamic reagent pool. , 2008, Angewandte Chemie.

[71]  G. F. Joyce,et al.  Self-Sustained Replication of an RNA Enzyme , 2009, Science.

[72]  N. Wagner,et al.  Self-replicating amphiphilic beta-sheet peptides. , 2009, Angewandte Chemie.

[73]  S. Otto,et al.  Transient substrate-induced catalyst formation in a dynamic molecular network. , 2014, Angewandte Chemie.

[74]  Sijbren Otto,et al.  Exponential self-replication enabled through a fibre elongation/breakage mechanism , 2015, Nature Communications.

[75]  Gerhard Klebe,et al.  Structure-based design of inhibitors of the aspartic protease endothiapepsin by exploiting dynamic combinatorial chemistry. , 2014, Angewandte Chemie.

[76]  Jessica K. Polka,et al.  Microtubule nucleating γTuSC assembles structures with 13-fold microtubule-like symmetry , 2010, Nature.

[77]  C. Lorenz,et al.  Elucidating the origin of diastereoselectivity in a self-replicating system: selfishness versus altruism. , 2011, Chemistry.

[78]  Laurent Vial,et al.  Dynamic combinatorial chemistry. , 2006, Chemical reviews.