Directed evolution of multivalent glycoclusters

Complex glyconjugates are usually rationally designed due to convenience and a lack of understanding of glycan structure-function. Krauss et al. describe, for the first time, a method for evolving glycans with novel binding properties. Basically, the authors make use of DNA which acts as a scaffold for presenting various glycans in multiple positions. Glycans are installed via 'click' chemistry, and accordingly the position of alkyne-modified nucleotides in the DNA sequence determines the position of these glycans. These unnatural nucleotides are easily randomly introduced into a template scaffold DNA by PCR. Thus, once a particular glycan has been identified through a binding selection, the DNA can be amplified and sequenced, revealing the identity of the multivalent glycan. This is very clever stuff, and I look forward to seeing more progress in the future!