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.
Green Jonathan E., Wook Choi Jang, Boukai Akram, Bunimovich Yuri, Johnston-Halperin Ezekiel, DeIonno Erica, Luo Yi, Sheriff Bonnie A., Xu Ke, Shik Shin Young, Tseng Hsian-Rong, Stoddart J. Fraser, Heath James R., A 160-kilobit molecular electronic memory patterned at 1011 bits per square centimetre, 10.1038/nature05462
Berná José, Leigh David A., Lubomska Monika, Mendoza Sandra M., Pérez Emilio M., Rudolf Petra, Teobaldi Gilberto, Zerbetto Francesco, Macroscopic transport by synthetic molecular machines, 10.1038/nmat1455
Eelkema Rienk, Pollard Michael M., Vicario Javier, Katsonis Nathalie, Ramon Blanca Serrano, Bastiaansen Cees W. M., Broer Dirk J., Feringa Ben L., Molecular machines: Nanomotor rotates microscale objects, 10.1038/440163a
Muraoka Takahiro, Kinbara Kazushi, Aida Takuzo, Mechanical twisting of a guest by a photoresponsive host, 10.1038/nature04635
Juluri Bala Krishna, Kumar Ajeet S., Liu Yi, Ye Tao, Yang Ying-Wei, Flood Amar H., Fang Lei, Stoddart J. Fraser, Weiss Paul S., Huang Tony Jun, A Mechanical Actuator Driven Electrochemically by Artificial Molecular Muscles, 10.1021/nn8002373
Thordarson Pall, Bijsterveld Edward J. A., Rowan Alan E., Nolte Roeland J. M., Epoxidation of polybutadiene by a topologically linked catalyst, 10.1038/nature01925
Monnereau Cyrille, Ramos Pilar Hidalgo, Deutman Alexander B. C., Elemans Johannes A. A. W., Nolte Roeland J. M., Rowan Alan E., Porphyrin Macrocyclic Catalysts for the Processive Oxidation of Polymer Substrates, 10.1021/ja908524x
Würthner Frank, Rebek Julius, Light-Switchable Catalysis in Synthetic Receptors, 10.1002/anie.199504461
Yoon H. J., Kuwabara J., Kim J.-H., Mirkin C. A., Allosteric Supramolecular Triple-Layer Catalysts, 10.1126/science.1193928
Schmittel Michael, De Soumen, Pramanik Susnata, Reversible ON/OFF Nanoswitch for Organocatalysis: Mimicking the Locking and Unlocking Operation of CaMKII, 10.1002/anie.201108089
Blanco Victor, Carlone Armando, Hänni Kevin D., Leigh David A., Lewandowski Bartosz, A Rotaxane-Based Switchable Organocatalyst, 10.1002/anie.201201364
Wang J., Feringa B. L., Dynamic Control of Chiral Space in a Catalytic Asymmetric Reaction Using a Molecular Motor, 10.1126/science.1199844
He Yu, Liu David R., Autonomous multistep organic synthesis in a single isothermal solution mediated by a DNA walker, 10.1038/nnano.2010.190
McKee Mireya L., Milnes Phillip J., Bath Jonathan, Stulz Eugen, Turberfield Andrew J., O'Reilly Rachel K., Multistep DNA-Templated Reactions for the Synthesis of Functional Sequence Controlled Oligomers, 10.1002/anie.201002721
McKee Mireya L., Milnes Phillip J., Bath Jonathan, Stulz Eugen, O’Reilly Rachel K., Turberfield Andrew J., Programmable One-Pot Multistep Organic Synthesis Using DNA Junctions, 10.1021/ja2101196
He Yu, Liu David R., A Sequential Strand-Displacement Strategy Enables Efficient Six-Step DNA-Templated Synthesis, 10.1021/ja201361t
Gu Hongzhou, Chao Jie, Xiao Shou-Jun, Seeman Nadrian C., A proximity-based programmable DNA nanoscale assembly line, 10.1038/nature09026
Sieber Stephan A., Marahiel Mohamed A., Molecular Mechanisms Underlying Nonribosomal Peptide Synthesis: Approaches to New Antibiotics, 10.1021/cr0301191
Aucagne Vincent, Hänni Kevin D., Leigh David A., Lusby Paul J., Walker D. Barney, Catalytic “Click” Rotaxanes: A Substoichiometric Metal-Template Pathway to Mechanically Interlocked Architectures, 10.1021/ja056903f
Crowley James D., Goldup Stephen M., Lee Ai-Lan, Leigh David A., McBurney Roy T., Active metal template synthesis of rotaxanes, catenanes and molecular shuttles, 10.1039/b804243h
Dawson P., Muir T., Clark-Lewis I, Kent S., Synthesis of proteins by native chemical ligation, 10.1126/science.7973629
Hansen Finn K., Ha Khanh, Todadze Ekaterina, Lillicotch Aaron, Frey Alexander, Katritzky Alan R., Microwave-assisted chemical ligation of S-acyl peptides containing non-terminal cysteine residues, 10.1039/c1ob05740e
Payne Richard J., Ficht Simon, Tang Sishi, Brik Ashraf, Yang Yu-Ying, Case David A., Wong Chi-Huey, Extended Sugar-Assisted Glycopeptide Ligations: Development, Scope, and Applications, 10.1021/ja073653p
Badi Nezha, Lutz Jean-François, Sequence control in polymer synthesis, 10.1039/b806413j
Berná José, Crowley James D., Goldup Stephen M., Hänni Kevin D., Lee Ai-Lan, Leigh David A., A Catalytic Palladium Active-Metal Template Pathway to [2]Rotaxanes, 10.1002/anie.200701678
Dewey R. S., Schoenewaldt E. F., Joshua H., Paleveda William J., Schwam H., Barkemeyer H., Arison Byron H., Veber Daniel F., Denkewalter Robert G., Hirschmann Ralph., Synthesis of peptides in aqueous medium. V. Preparation and use of 2,5-thiazolidinediones (NTA's). Use of the 13C-H nuclear magnetic resonance signal as internal standard for quantitative studies, 10.1021/ja01014a059
Biegel Annegret, Gebauer Sabine, Hartrodt Bianka, Brandsch Matthias, Neubert Klaus, Thondorf Iris, Three-Dimensional Quantitative Structure−Activity Relationship Analyses of β-Lactam Antibiotics and Tripeptides as Substrates of the Mammalian H+/Peptide Cotransporter PEPT1, 10.1021/jm048982w
Bibliographic reference
Lewandowski, B. ; De Bo, G. ; Ward, J. W. ; Papmeyer, M. ; Kuschel, S. ; et. al. Sequence-Specific Peptide Synthesis by an Artificial Small-Molecule Machine. In: Science, Vol. 339, no. 6116, p. 189-193 (2013)