The ribosome is a biological molecular machine and is responsible for the sequence-specific synthesis of proteins; it binds to and travels along an mRNA strand in order to assemble reactive tRNA building blocks in a precise sequence determined by genetic information transcribed from DNA. We report the synthesis and operation of a three barrier, artificial molecular machine capable of travelling along a molecular thread, picking up amino acids that block its path, in turn synthesizing a beta-homo (β3) peptide in a sequence-specific manner. The machine is rotaxane based and consists of a thread and a macrocycle. The macrocyle carries a thiolate group that iteratively removes amino acids (which also act as barriers) in order from the thread and transfers them to a growing peptide chain via native chemical ligation (NCL). The machine utilizes non-proteinogenic β3-amino acids, a class of amino acids not generally accepted by the natural ribosome. Successful operation of this machine demonstrates that the challenging 15- and 19- membered ligation transition states, which have been previously unexplored in machina, are suitable for information translation via machine operation. Furthermore, by employing peptidases, a class of naturally occurring biological machines, we demonstrate that artificial and natural machines can work in concert to generate products currently inaccessible by either strategy alone.

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

254th National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.