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

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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 ~10(18) 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
    JournalScience (New York, NY)
    Issue number6116
    Publication statusPublished - 2013


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