1421686-41-0Relevant academic research and scientific papers
Sequence-Selective Decapeptide Synthesis by the Parallel Operation of Two Artificial Molecular Machines
Echavarren, Javier,Gall, Malcolm A. Y.,Haertsch, Adrian,Leigh, David A.,Spence, Justin T. J.,Tetlow, Daniel J.,Tian, Chong
supporting information, p. 5158 - 5165 (2021/05/04)
We report on the preparation of a decapeptide through the parallel operation of two rotaxane-based molecular machines. The synthesis proceeds in four stages: (1) simultaneous operation of two molecular peptide synthesizers in the same reaction vessel; (2) selective residue activation of short-oligomer intermediates; (3) ligation; (4) product release. Key features of the machine design include the following: (a) selective transformation of a thioproline building block to a cysteine (once it has been incorporated into a hexapeptide intermediate by one molecular machine); (b) a macrocycle-peptide hydrazine linkage (as part of the second machine) to differentiate the intermediates and enable their directional ligation; and (c) incorporation of a Glu residue in the assembly module of one machine to enable release of the final product while simultaneously removing part of the assembly machinery from the product. The two molecular machines participate in the synthesis of a product that is beyond the capability of individual small-molecule machines, in a manner reminiscent of the ligation and post-translational modification of proteins in biology.
Sequence-specific peptide synthesis by an artificial small-molecule machine
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.
, p. 189 - 193 (2013/03/14)
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.
