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

Bartosz Lewandowski, Guillaume De Bo, John W. Ward, Marcus Papmeyer, Sonja Kuschel, María J. Aldegunde, Philipp M.E. Gramlich, Dominik Heckmann, Stephen M. Goldup, Daniel M. D'Souza, Antony E. Fernandes, David A. Leigh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

542 Citations (Scopus)


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 ∼1018 molecular machines acting in parallel; this process generates milligram quantities of a peptide with a single sequence confirmed by tandem mass spectrometry.

Original languageEnglish
Pages (from-to)189-193
Number of pages5
Issue number6116
Publication statusPublished - 11 Jan 2013

ASJC Scopus subject areas

  • General


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