Haemagglutinin (HA) Multimers

David Nowack (Chemistry)

Haemagglutinin (HA) Multimers as Probes for the Detection of 2,3- and 2,6- Sialic Acid Bond Structures

The research collaboration between the Van Andel Institute in Grand Rapids, MI and Andrews University, previously and continuing, is designed to discover sialic acid changes associated with pancreatic cancer. During the preliminary investigations as the collaboration began for this project, it soon became evident that the technology required to find the sialic acid changes was inadequate in specificity and reproducibility. Thus, the current project, as listed in the title, was begun to discover more specific probes that identify the sialic acid targets more effectively. An overview of the current project is the following:

The carbohydrate (CHO) moieties attached to glycoproteins are proving to be important loci for detection and regulation of cellular activity. Changes to the CHO moieties are linked to the presence of pre-cancerous and cancerous changes in the cells and tissues. In particular, changes in sialic acid bonds between 2,3 and 2,6 linkages may be important indicators of disease, but unfortunately an effective way of precisely measuring these linkages in biological samples does not yet exist.  The various HA proteins (bird flu, swine flu, human flu) bind to 2,3- and 2,6-sialic acid bonds as a preliminary step for infection within the host. We hypothesized that HA proteins could be used to detect specific presentations of sialic acid moieties on glycoproteins captured from biological samples. In this study we used a simple method of multimerizing the HA protein to increase its binding avidity, and applied the HA proteins to the detection of sialic acids on biological glycoproteins. Using that specificity to detect changes in glycoprotein CHO structures, we discovered that the HA probes can differentiate between 2,3- and 2,6- sialic acid bond types in an efficient and reproducible manner. Studies also are underway to determine the relationship between sialic acid linkages and the presence of pancreatic cancer. This approach may provide robust and sensitive measurements of specific sialic acid presentations in biological samples.

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