Armin Benz and Jörg Hartig from the University of Konstanz have used guanosine analogs to control the topology of G-quadruplexes. 

'G-rich nucleic acids are prone to fold into four-stranded structures called quadruplexes. These unusual conformations are suspected to play important roles in our genomes' says Hartig. 'With respect to the function inside our cells, it would be very interesting to know which conformations are adopted. Most likely, different conformations have different properties but we lack the tools to study the differences since we are not able to control the individual conformations.' 

This new strategy allows Hartig and Benz to program quadruplexes to adopt a distinct topology. 'The modified nucleosides assemble into tetrads but do not mix with the natural guanosines' Hartig explains. 'Under conditions where the natural sequence adopts a mixture of differently folded species, we are able to restrict the possible conformations to the wanted one.' 

Hartig says that this approach should be useful for studying properties of individual folds that are otherwise inaccessible. 'The investigation of programmed quadruplex conformations under varying conditions should contribute to the understanding of the various stabilizing forces contributing to quadruplex formation.' 

Rachel Cooper.