title: Theoretical Analysis of a Self-Replicator With Reduced Template Inhibition Based on an Informational Leaving Group.
abstract: The first non-enzymatic self-replicating systems, as proposed by von Kiedrowski (Angew Chem Int Ed Engl 25(10):932-935, 1986) and Orgel (Nature 327(6120):346-347, 1987), gave rise to the analytical background still used today to describe artificial replicators. What separates a self-replicating from an autocatalytic system is the ability to pass on structural information (Orgel, Nature 358(6383):203-209, 1992). Utilising molecular information, nucleic acids were the first choice as prototypical examples. But early self-replicators showed parabolic over exponential growth due to the strongly bound template duplex after template-directed ligation of substrates. We propose a self-replicating scheme with a weakly bound template duplex, using an informational leaving group. Such a scheme is inspired by the role of tRNA as leaving group and information carrier during protein synthesis, and is based on our previous experience with nucleotide chemistry. We analyse theoretically this scheme and compare it to the classical minimal replicator model. We show that for an example hexanucleotide template mirroring that is used by von Kiedrowski (Bioorganic chemistry frontiers, 1993) for the analysis of the classical minimal replicator, the proposed scheme is expected to result in higher template self-replication rate. The proposed self-replicating scheme based on an informational leaving group is expected to outperform the classical minimal replicator because of a weaker template duplex bonding, resulting in reduced template inhibition.
authors.affiliation: Laboratoire d'Informatique (LIX), École Polytechnique, 91128, Palaiseau Cedex, France.|Laboratoire Matière et Systèmes Complexes, UMR7057 CNRS, Université Paris Diderot, 75205, Paris Cedex 13, France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Bigan
authors.affiliation: Laboratory of Medicinal Chemistry, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, 3000, Leuven, Belgium.
authors.forename: Henri-Philippe
authors.initials: HP
authors.lastname: Mattelaer
authors.affiliation: Laboratory of Medicinal Chemistry, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, 3000, Leuven, Belgium. chantal.biernaux@rega.kuleuven.be.
authors.forename: Piet
authors.initials: P
authors.lastname: Herdewijn
mesh_terms: D004261:DNA Replication / Q000502:physiology*; D008957:Models, Genetic; D009696:Nucleic Acids; D009841:Oligonucleotides; D000069497:Origin of Life; D013698:Templates, Genetic
chemical_list: D009696:Nucleic Acids; D009841:Oligonucleotides
keywords: Autocatalysis; Informational leaving group model; Minimal replicator; Oligonucleotide; Self-replication; Template inhibition