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

Sequence-specific peptide synthesis by an artificial small-molecule machine
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 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.
0036-8075
189-193
Lewandowski, B.
308b6cf6-8221-4924-ac8d-8f980baf13ec
De Bo, G.
64561541-d056-4924-bf24-996a5d3e973f
Ward, J.W.
91c735ad-544d-4b98-bca0-a5a4271c0d6c
Papmeyer, M.
0d01fba5-0b06-4d04-8f21-1b4106751908
Kuschel, S.
401ed0d4-f8e4-4a3b-bbc5-13a6117f769b
Aldegunde, M.J.
699ff78c-d565-4114-9602-2244c6d9d479
Gramlich, P.M.E.
58edd0d8-90a4-4d3b-993a-f8828b506712
Heckmann, D.
778db127-2b09-4928-a2cf-803b7cfb68c9
Goldup, S.M.
0a93eedd-98bb-42c1-a963-e2815665e937
D'Souza, D.M.
c8cb3fae-e387-4bd3-bbca-6db3c73fd276
Fernandes, A.E.
efe481a9-c210-4706-9cf2-6ca2548b0d98
Leigh, D.A.
b8bd29df-f8ea-4b96-a72f-982435eb0604
Lewandowski, B.
308b6cf6-8221-4924-ac8d-8f980baf13ec
De Bo, G.
64561541-d056-4924-bf24-996a5d3e973f
Ward, J.W.
91c735ad-544d-4b98-bca0-a5a4271c0d6c
Papmeyer, M.
0d01fba5-0b06-4d04-8f21-1b4106751908
Kuschel, S.
401ed0d4-f8e4-4a3b-bbc5-13a6117f769b
Aldegunde, M.J.
699ff78c-d565-4114-9602-2244c6d9d479
Gramlich, P.M.E.
58edd0d8-90a4-4d3b-993a-f8828b506712
Heckmann, D.
778db127-2b09-4928-a2cf-803b7cfb68c9
Goldup, S.M.
0a93eedd-98bb-42c1-a963-e2815665e937
D'Souza, D.M.
c8cb3fae-e387-4bd3-bbca-6db3c73fd276
Fernandes, A.E.
efe481a9-c210-4706-9cf2-6ca2548b0d98
Leigh, D.A.
b8bd29df-f8ea-4b96-a72f-982435eb0604

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)

Record type: Article

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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More information

Published date: 11 January 2013
Organisations: Organic Chemistry: Synthesis, Catalysis and Flow

Identifiers

Local EPrints ID: 370650
URI: http://eprints.soton.ac.uk/id/eprint/370650
ISSN: 0036-8075
PURE UUID: 3b7155e9-901d-4942-a19d-b773f8330629
ORCID for S.M. Goldup: ORCID iD orcid.org/0000-0003-3781-0464

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Date deposited: 03 Nov 2014 12:57
Last modified: 14 Mar 2024 18:19

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Contributors

Author: B. Lewandowski
Author: G. De Bo
Author: J.W. Ward
Author: M. Papmeyer
Author: S. Kuschel
Author: M.J. Aldegunde
Author: P.M.E. Gramlich
Author: D. Heckmann
Author: S.M. Goldup ORCID iD
Author: D.M. D'Souza
Author: A.E. Fernandes
Author: D.A. Leigh

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