Sequence-specific peptide synthesis by an artificial small-molecule machine

Science. 2013 Jan 11;339(6116):189-93. doi: 10.1126/science.1229753.

Abstract

The ribosome builds proteins by joining together amino acids in an order determined by messenger RNA. Here, we report on the design, synthesis, and operation of an artificial small-molecule machine that travels along a molecular strand, picking up amino acids that block its path, to synthesize a peptide in a sequence-specific manner. The chemical structure is based on a rotaxane, a molecular ring threaded onto a molecular axle. The ring carries a thiolate group that iteratively removes amino acids in order from the strand and transfers them to a peptide-elongation site through native chemical ligation. The synthesis is demonstrated with ~10(18) molecular machines acting in parallel; this process generates milligram quantities of a peptide with a single sequence confirmed by tandem mass spectrometry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence*
  • Chemical Phenomena
  • Chemistry Techniques, Synthetic*
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptides / chemical synthesis*
  • Peptides / chemistry*
  • Rotaxanes / chemistry*
  • Tandem Mass Spectrometry

Substances

  • Peptides
  • Rotaxanes