title: Sequence-specific peptide synthesis by an artificial small-molecule machine.
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 ~10(18) molecular machines acting in parallel; this process generates milligram quantities of a peptide with a single sequence confirmed by tandem mass spectrometry.
authors: School of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, UK.
authors: Bartosz
authors: B
authors: Lewandowski
authors: Guillaume
authors: G
authors: De Bo
authors: John W
authors: JW
authors: Ward
authors: Marcus
authors: M
authors: Papmeyer
authors: Sonja
authors: S
authors: Kuschel
authors: María J
authors: MJ
authors: Aldegunde
authors: Philipp M E
authors: PM
authors: Gramlich
authors: Dominik
authors: D
authors: Heckmann
authors: Stephen M
authors: SM
authors: Goldup
authors: Daniel M
authors: DM
authors: D'Souza
authors: Antony E
authors: AE
authors: Fernandes
authors: David A
authors: DA
authors: Leigh
mesh_terms: D000595:Amino Acid Sequence; D055598:Chemical Phenomena; D060326:Chemistry Techniques, Synthetic; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D043862:Rotaxanes / Q000737:chemistry*; D053719:Tandem Mass Spectrometry
chemical_list: D010455:Peptides; D043862:Rotaxanes