Chemists synthesize molecular pretzels

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Chemists at the University of Amsterdam’s Van’t Hoff Institute for Molecular Sciences have found a new class of molecules. This week they reported in Nature Communications on their synthesis method leading to ‘quasi catenanes’ pretzel-like molecules comprising of two molecular rings ‘oppositely’ coupled at a central carbon atom. The discovery is vital milestone towards synthesis of lasso peptides; new molecules with a potential use as medicines.

The Nature Communication article is the crowning achievement of a five-year research effort at the Synthetic Organic Chemistry research group of professor Jan van Maarseveen, with PhD student Luuk Stemers in the lead. He has developed a technique which paves the way for synthesis of so-called lasso peptides.

 

Lasso peptides are small proteins which comprise of a molecular ‘loop’ around a molecular ‘rope’. They were first isolated from bacteria at the turn of the current century. Recently, DNA analysis has showed that lasso peptides are relatively common in the bacteria realm. Their biological function is to act as an antibiotic against other micro-organisms, which makes them a potential new class of antibiotics.

The tailback here is that the rope is usually tightly bound within the loop. This distinguishes lasso peptides from rotaxanes for which Scottish chemist Sir Fraser Stoddart shared the Nobel prize for chemistry last year. During rotaxane synthesis the rope is ‘pulled’ through the loop. Since this is impossible for lasso peptide synthesis, the Amsterdam chemists used a different method, forcing the loop to close in the right place around the rope. Eventually Luuk Stemers succeeded to develop a molecular scaffold aiding the synthesis through the loop correctly forming around the rope.

The new synthesis method is a huge step forward in the synthetic route towards functional lasso peptides. To demonstrate the power of the method Stemers applied his scaffold to also force both ends of the rope to form a second loop.

Source: Nature.com

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