A new paper in Angewandte Chemie International Edition from a Brandeis group led by postdoc Iain MacPherson, Professor of Biology Liz Hedstrom and Assistant Professor of Chemistry Isaac Krauss introduces a new technique they dub SELMA, short for “selection with modified aptamers”. Currently available selection methods can identify the few oligonucleotides in a library of 107 random DNAs or RNAs that bind specifically to a target protein (these specific binders are termed aptamers). However, nucleic acids have a very limited repertoire of chemical functionality — SELMA expands this functionality by introducing an alkyne-modified nucleotide that can be coupled to virtually any azide-containing compound using a copper catalyzed azide-alkyne cycloaddition reaction (“click chemistry“).
The Brandeis group used SELMA to create a library of sugar-modified oligonucleotides and selected for glycoclusters that mimic the epitope of 2G12, an antibody that protects against HIV infection by binding to a cluster of high-mannose glycans on the HIV envelope protein gp120. This is the first example of the application of directed evolution to protein-carbohydrate interactions, a particularly difficult class of interactions to mimic with traditional synthetic methods. Protein carbohydrate interactions are involved in wide array of biological processes, including cell-cell signaling, cell migration and developmental programming as well as immune recognition, so this method should prove very useful.
MacPherson, I. S., Temme, J. S., Habeshian, S., Felczak, K., Pankiewicz, K., Hedstrom, L. and Krauss, I. J. (2011), Multivalent Glycocluster Design through Directed Evolution. Angewandte Chemie International Edition, 50: 11238–11242. doi: 10.1002/anie.201105555