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

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 pep...

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Vydáno v:Science (American Association for the Advancement of Science) Ročník 339; číslo 6116; s. 189
Hlavní autoři: Lewandowski, Bartosz, De Bo, Guillaume, Ward, John W, Papmeyer, Marcus, Kuschel, Sonja, Aldegunde, María J, Gramlich, Philipp M E, Heckmann, Dominik, Goldup, Stephen M, D'Souza, Daniel M, Fernandes, Antony E, Leigh, David A
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 11.01.2013
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ISSN:1095-9203, 1095-9203
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Shrnutí: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.
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ISSN:1095-9203
1095-9203
DOI:10.1126/science.1229753