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Nature's molecular factories

A ribosome can churn out identical proteins according to the structure of the template messenger RNA. Mimicking multiple translation in a reaction vessel is the synthetic chemist's dream and could lead to designer protein production on a massive scale.
Nature's molecular factories
Various research groups have built 'molecular factories', one recently based on rotaxane, a dumbbell-shaped molecule, threaded through a macrocycle. A circular molecule, the macrocycle acts as both a catalyst and a molecular transporter. However, limitations include the deletion of the sequence as it is translated.

The RELOADPEPSYN (A reloadable molecular peptide synthesizer) project has constructed a synthetic molecular machine that incorporates a reloadable track strategy. Thus, in principle, longer peptide chains than have previously been possible can be synthesised and the machine itself can be usable multiple times.

Clever design means the macrocycle is forced to approach and detach each building block in a specific sequence along the 'thread' and then transfer it to the next building block to enable the formation of a covalent bond between the two. This results in sequential integrity of the new multi-block growing protein. The interlocking nature of rotaxane also allows the locking on of the macrocycle without dissociation.

After a series of optimisation reactions a rotaxane-based machine that was loaded with two amino acids was constructed in satisfactory yields. Mass spectrometry analyses showed that the two amino acids were incorporated into the growing chain and that they were in the correct order.

A reloadable machine, such as the RELOADPEPSYN machine, is potentially a major advance in the field. Examples of nanobiotech materials based on peptides range from detergents to replacement of damaged tissues and faulty enzymes as well as extra lung tissue to increase oxygen supply to the body.

Related information

Keywords

Molecular factories, protein production, rotaxane, RELOADPEPSYN, peptide synthesizer
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