11 January 2013

Man-made ribosome: the beginning is laid

An artificial ribosome analogue has been created

Kirill Stasevich, Compulenta

One of the most amazing engineering achievements of evolution is the ribosome, an RNA–protein machine that turns the genetic code into a polypeptide chain. Scientists from the University of Manchester (UK), led by Dave Lee, managed to get a completely artificial analogue of this wonderful machine: their nanodevice also produces a polymer in accordance with some instructions.

The ribosome was replaced by a rotaxan molecule for chemists. Rotaxanes are rather strange and unusual molecules. They consist of two parts: one part is the ring molecule, the other is the axis molecule on which the ring is worn. In order for it to hold, the axis molecule is made to look like a dumbbell, providing it with two "bulges" at the edges. The ring can rotate around an axis and move from one edge to the other: there is no rigid chemical bond between them.


The scheme of the rotaxane "ribosome" (figure of the authors of the work).

The researchers added three amino acids sequentially to the axial part, which did not allow the ring to slip off. Three amino acids were also attached to the ring, but in the form of a chain. This three-amino acid chain on the ring was a working "hand": the last one in it was cysteine with an active sulfur-containing thiol (or sulfhydryl) group. When heated, the thiol group transferred the amino acid to the ring, more precisely, to the end of the amino acid arm attached to the ring. Thus, the polypeptide sequence lengthened itself, using the ring as a support.

After the "hand" collected all the amino acids from the axis, the ring slipped off it, and the "hand" itself could be detached from the ring. An oligopeptide molecule was obtained in which the three extreme amino acids stood in the sequence in which they were placed on the axis. It is not difficult to point out the differences from the ribosome: in the rotaxane system, the code is simply a sequence in which it meets new raw materials; there is no such complex decoding as in biosynthesis. In addition, the "code" itself is destroyed here (amino acids are cleaned off the matrix axis), and the whole process is quite slow. It took hours and almost days to synthesize a peptide using such a system, whereas the ribosome synthesizes proteins at a rate of 15-20 amino acids per second. Not to mention the fact that the rotaxane "ribosome" serves only once and synthesizes only one peptide, after which it disintegrates.

On the other hand, we should not forget that, for example, airplanes once began with poor winged devices that flew not far and not for long. Researchers believe that the rotaxane machine may become even more efficient in the future than conventional (and faster) synthesis methods: peptides obtained with rotaxane are easier to clean and isolate. And, of course, we must not forget about the fundamental importance of the results, which will help to better understand how molecular machines work.

The transfer of amino acids using sulfhydryl groups is not an invention of chemists: some bacteria use this reaction. On the other hand, rotaxane molecules have long attracted scientists precisely as a tool for encoding and storing information, as well as as regulators of chemical reactions that turn on or off other catalyst molecules.

The research report was published in the journal Science: Lewandowski et al., Sequence-Specific Peptide Synthesis by an Artificial Small-Molecule Machine.

Prepared based on the materials of the University of Manchester: Molecular machine could hold the key to more efficient manufacturing.

Portal "Eternal youth" http://vechnayamolodost.ru11.01.2013

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