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

Lewandowski, B., De Bo, G., Ward, J.W., Papmeyer, M., Kuschel, S., Aldegunde, M.J., Gramlich, P.M.E., Heckmann, D., Goldup, S.M., D'Souza, D.M., Fernandes, A.E. and Leigh, D.A. (2013) Sequence-specific peptide synthesis by an artificial small-molecule machine. Science, 339 (6116), 189-193. (doi:10.1126/science.1229753). (PMID:23307739)

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 ~1018 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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Contributors

Author: S.M. Goldup

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