The longest oligourea foldamer: 4,3 nanometers

IECB team leader Dr. Gilles Guichard and his team (CBMN) have developed a new synthesis methodology to produce long urea-based foldamers. Previously, these objects could hardly be composed of more than 10 building blocks. Through a “clip” system, the Guichard team has managed to make the first oligourea foldamer made of 20 building blocks. This technical breakthrough, which was published in Angewandte Chemie International Edition, is expected expand the field of application of such folded architectures.

Artificial oligomers made of urea can mimic some if the α-helix structures that can be found in proteins. Labeled as “foldamers”, those peptidomimetic architectures can interact with biological macromolecules. In 2006, Gilles Guichard showed that some of the foldamers designed his lab were holding antimicrobial properties.

However, up to now, the size of these artificial molecules was a limiting factor. In order to mimic larger helixes, Dr. Gilles Guichard embarked on the development of a new synthesis technique.
He explains: “Our basic technique consists in adding our building blocks one-by-one, exactly as you would do with pearls to make a necklace. Such a technique does not allow us to constitute chains that exceed 10 or 12 building blocks. What we managed to demonstrate here, is that it is possible to produce longer chains by assembling “ready-made” segments via a “clip” system. Pyrrolidine, which we use as a joint between the segments, is compatible with the formation of helices. In the end, we characterized 5 helices of different dimension through X-ray diffraction, including a foldamer composed of 20 building blocks”.

IIIIIIIIIIIIIIIIIIIIIIIIIAbove, the 5 foldamers that were caracterized by the Guichard team at IECB.
//////      /////The smallest is 1,5-nanometer-long and is made of 7 building blocks.
////////// //The longest reach 4,3 nanometers and is composed of 20 building blocks

Lire l'article: Fremaux J., Fischer L.,  Arbogast T., Kauffmann B., Guichard G. (2011) Condensation Approach to Aliphatic Oligourea Foldamers: Helices with N-(pyrrolidin-2-ylmethyl)ureido Junctions, Ang. Chem. Int. Ed., DOI: 10.1002/anie.201105416