Peptide Morse code
: α/β-peptide β-sheets for information storage and transmission

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)

Abstract

The origin of life remains a most relevant scientific problem. It is clear that present-day life results from Darwinian evolution. However, in a prebiotic Earth, species (presumably molecules) capable of “informational self-replication” were necessary for evolution to be triggered. In this context, we propose a system based on α/β-peptide hybrid β-sheets. In these molecules, information can be encoded in the sequence of α- and β-amino acids. Aggregation into β-sheets should occur sequence-selectively and the aggregate can then act as a template for peptide self-replication. The use of long/short components to store and transfer information suggests the term “peptide Morse code” (PMC) for the system.

To prove this concept, we took two approaches: First, to study the sequence-selectivity of β-sheet formation, we used a series of short decamer α/β-peptide hybrids containing a β-turn segment. It was shown through NMR and CD analyses that molecules with matching α/β-residues in their β-strands would fold into stable β-hairpins in organic media, due to the formation of an intramolecular β-sheet, whereas, there was structural evidence for the absence of such stable intramolecular β-sheets in molecules bearing strands with mismatching α/β-residues. Secondly, to evaluate sequence-selective self-replication in α/β-peptide hybrids, we built a water-soluble amphiphilic PMC variant of a literature replicator and an alternative hydrophobic system. Unfortunately, autocatalysis has remained elusive in both peptide systems. Alternatively, evidence for the intramolecular templation of new covalent bonds arising from α/β-sequence recognition in the strands of a β-hairpin was obtained.

This work has provided the first evidence for both, the α/β-sequence-selective assembly of β-sheet structures and the template-directed formation of covalent bonds by these structures.
Date of Award23 Jun 2020
Original languageEnglish
Awarding Institution
  • The University of Bristol
SponsorsCONACyT
SupervisorJonathan P Clayden (Supervisor) & Anthony P Davis (Supervisor)

Keywords

  • Origin of life
  • peptide secondary structure

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