A Synthetic Molecular Machine Capable of Complex T.. ('Ribosome MM')
A Synthetic Molecular Machine Capable of Complex Task Performance: Processive Sequence-Selective Synthesis
Start date: Mar 1, 2009,
End date: Feb 28, 2011
The aim of this proposal is to synthesize and demonstrate the successful operation of one of the first synthetic molecular machines capable of performing a complex task at the molecular level. The target is to mimic translation, the process through which protein is synthesized on the mRNA template in the ribosome. To achieve this ambitious task (in a very basic form) through the action of a wholly artificial molecular machine system we propose to utilize a rotaxane in which the macrocycle component acts as both a catalyst and a molecular transporter, abstracting bulky aromatic amino acid substituents from a sequence-specific ‘thread’ and transporting them in turn to the next amino acid fragment before mediating the formation of a new amide bond between them. The design is such that the macrocycle is forced to approach each amino acid in sequence, and is unable to pass until the cycle is complete, imparting sequential integrity to the oligopeptide synthesis. The mechanically interlocked nature of the rotaxane ensures processivity during the machine’s operation. Although biology uses threaded molecular architectures to transfer chemical information during sequence-specific oligomer and polymer assembly (proteins, oligo- and polysaccharides, DNA and RNA), such effects are unprecedented in artificial systems. We hope that our synthetic studies will provide a breakthrough in the development of artificial molecular machines that can perform real tasks at the molecular level including, ultimately, the synthesis of unnatural sequence-specific oligomers and polymers that are not accessible by other routes.
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