Journal
SCIENCE
Volume 339, Issue 6116, Pages 189-193Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1229753
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Funding
- Engineering and Physical Sciences Research Council (UK)
- Fundacja na Rzecz Nauki Polskiej
- Fonds de la Recherche Scientifique
- Wallonie-Bruxelles International
- European Union
- Deutscher Akademischer Austausch Dienst
- Deutsche Akademia der Naturforscher Leopoldina
- Peter und Traudl Engelhorn-Stiftung
- EPSRC [EP/H021620/1, EP/H021620/2] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [EP/H021620/1, EP/H021620/2] Funding Source: researchfish
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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 similar to 10(18) molecular machines acting in parallel; this process generates milligram quantities of a peptide with a single sequence confirmed by tandem mass spectrometry.
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