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Uncovering the selection criteria for the emergence of multi-building-block replicators from dynamic combinatorial libraries

Malakoutikhah, M., Peyralans, J. J-P., Colomb-Delsuc, M., Fanlo-Virgós, H., Stuart, M. C. A. & Otto, S., 11-Dec-2013, In : Journal of the American Chemical Society. 135, 49, p. 18406-18417 12 p.

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DOI

A family of self-replicating macrocycles was developed using dynamic combinatorial chemistry. Replication is driven by self-assembly of the replicators into fibrils and relies critically on mechanically induced fibril fragmentation. Analysis of separate dynamic combinatorial libraries made from one of six peptide-functionalized building blocks of different hydrophobicity revealed two selection criteria that govern the emergence of replicators from these systems. First, the replicators need to have a critical macrocycle size that endows them with sufficient multivalency to enable their self-assembly into fibrils. Second, efficient replication occurs only for library members that are of low abundance in the absence of a replication pathway. This work has led to spontaneous emergence of replicators with unrivalled structural complexity, being built from up to eight identical subunits and reaching a MW of up to 5.6 kDa. The insights obtained in this work provide valuable guidance that should facilitate future discovery of new complex self-replicating molecules. They may also assist in the development of new self-synthesizing materials, where self-assembly drives the synthesis of the very molecules that self-assemble. To illustrate the potential of this concept, the present system enables access to self-assembling materials made from self-synthesizing macrocycles with tunable ring size ranging from trimers to octamers.

Original languageEnglish
Pages (from-to)18406-18417
Number of pages12
JournalJournal of the American Chemical Society
Volume135
Issue number49
Publication statusPublished - 11-Dec-2013

    Keywords

  • PEPTIDE SELF-REPLICATION, DEPENDENT EXPONENTIAL AMPLIFICATION, DIELS-ALDER REACTION, SUPRAMOLECULAR CHEMISTRY, AROMATIC INTERACTIONS, SYNTHETIC REPLICATOR, FIBRIL FORMATION, CROSS-CATALYSIS, LIGASE RIBOZYME, RNA ENZYME

ID: 6008431