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Synthetic capsules made from natural building blocks have been studied with NMR spectroscopy. The block copolymer capsules made from protein and sugar components mimic the behaviour of cells and might be useful as microreactors or as drug-delivery agents. Life exists because of vesicles. Vesicles are like microscopic bubbles, a membrane comprised of lipids, proteins, and carbohydrates, encloses, a liquid-filled space within which biochemistry can take place protected from the external world. In one sense, living cells are nothing more than very big vesicles. However, small vesicles play a critical role in the intracellular transport of biomolecules. Researchers have spent decades trying to create synthetic vesicles with some of the properties of cells and natural vesicles. Indeed, since at least the 1960s, artificial and natural materials have been used to create the necessary membranes and liposomes, made of lipids, have even reached commercialisation. These synthetic vesicles are commonly used to transport active ingredients in products such as cosmetic and pharmaceutical formulations. "The development of polymersomes, polymer made vesicles, over the last ten years offer promising advantages compared to liposomes, such as high stability and loading and chemical versatility," Sébastien Lecommandoux, of the Université de Bordeaux, Pessac, France, told SpectroscopyNOW. Vesicles have much greater potential than their simple face value might suggest. Lecommandoux and colleagues, Christophe Schatz, Stéphanie Louguet, and Jean-François Le Meins, explain in the current issue of Angewandte Chemie how vesicles could be used as microreactors that mimic the behaviour of living cells but allow chemists to carry out their own reactions within. The researchers point out that mimicking cells would be more successful if instead of using polymers, they could use more natural components. The team has now linked together blocks of sugar molecule chains (polysaccharides) and short chunks of protein-like chains (polypeptides) in a linear fashion. In water, these block copolymers spontaneously form vesicles, the team says. The researchers used dextran, a polymer made of glucose building blocks, and poly(benzyl L-glutamate) (PBLG), a biocompatible polypeptide. By exploiting the synthetic reaction scheme invented by Scripps' Nobel laureate Barry Sharpless and colleagues known as "click chemistry", the French team could build the structures brick by brick. Sharpless introduced the "click chemistry" concept of synthetic chemistry in 2001 and describes it as chemistry tailored to generating substances quickly and reliably by joining small units together. The approach was inspired by the fact that nature works in this way by clicking together small modular units. Click chemistry has the advantage of allowing them to construct their semi-synthetic vesicles under rather mild reaction conditions, instead of potentially damaging high temperatures. They obtained almost quantitative yields of the products, which means less waste and a more time efficient process. They point out that the other functional side groups on the reactant molecules simply do not interfere with the main reaction thanks to the click chemistry approach. In this way, the scientists produced block copolymers that combine a polypeptide (protein-like) block and a sugar block. The hydrophobic (water-repellant) polypeptide adopts a helical conformation and in water solutions prefers to be side-to-side with those like itself. This phenomenon results in the formation of membrane-like layers that close in on themselves to form the desired spherical vesicles. On both sides of the synthetic membrane, the hydrophilic (water-friendly) dextran chains coil up into a stabilizing "corona". The team used electron microscopy to take a close look at their membranes and measured them at just 21 nanometres thick and forming vesicles of uniform size, about 45 nm radius. Now that they have demonstrated proof of principle, the next step is to use the simple, but versatile, synthetic strategy to make other synthetic glycopeptides that could be used as model compounds for the exploration of cellular sugar structures (glycomics). The researchers also explain that the vesicles could be used in drug and gene transport because their sugar "corona" binds well to glycoproteins on the surfaces of living cells. "We believe that the proposed synthetic strategy, owing to its ease and versatility, could probably be applied to a large range of polypeptide and polysaccharide molecules of biological interest, such as polysialic acid or hyaluronic acid. Hence, the development of polysaccharide-block-polypeptide copolymers may play a significant role in future applications of polymers in biology," the team concludes. Related links: The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.
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 Natural-synthetic capsules made with click chemistry
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