Soluble dendrimers have been used to study differences in protein abundance in complex snake venoms. 

Quantitative proteomics is used to detect differences in the protein profiles of cells or tissues in different states, and is becoming an increasingly important technique for biomarker and disease discovery. A common approach for this is to use a solid phase reagent to simultaneously capture and label proteins in solution for analysis. 

Andy Tao and colleagues at Purdue University, West Lafayette, have developed a new strategy for quantitative proteomics called soluble polymer-based isotopic labelling (SoPIL). They used the technique to quantify differences in protein levels and enzyme activity between two different samples of snake venom. Snake venoms contain complex mixtures of proteins and other pharmacologically active molecules. According to Tao, they could be useful tools for drug discovery. 

A soluble dendrimer (blue) delivers an isotope tag (X) to cysteine-containing proteins

Tao's method uses a polymer, a soluble dendrimer, to bind and deliver an isotope label to proteins containing the amino acid cysteine within a solution mixture. An alkyne group on the dendrimer then acts as a handle to join the proteins to a solid phase reagent, allowing them to be removed easily from the solution. The tagged proteins can then be released from the solid and analysed by mass spectrometry. Compared to the established single-step solid phase capture and tagging method, the SoPIL two-step strategy produced labelled proteins much more quickly, and isolated the target protein in a higher yield.

Lingjun Li, an expert in mass-spectrometry-based protein analysis from the University of Wisconsin, Madison, US, explained that the SoPIL method could have many uses in proteomics research. By choosing different reactive handle groups, a wide range of applications, including probing various protein modifications in biological systems, should be possible, she said. 

According to Tao, the soluble dendrimers also offer potential for in vivo proteomics. This would give a more accurate indication of the proteins in the living cell, as it is not known how physically disrupting cells for in vitro analysis affects their protein concentrations and distributions, he said. 

Katherine Vickers