We report covalently coupled immunostimulant heterodimers synthesized at discrete molecular distances, and subsequent activation of dendritic cells. Many vaccines present spatially organized agonists to immune cell receptors. These receptors cluster suggesting that signaling is increased by spatial organization and receptor proximity, but this has not been directly tested for multiple, unique receptors. In this study we probe the spatial aspects of immune cell activation using heterodimers of a variety of covalently attached immunostimulants including imidazoquinolines, pyrimido[5,4 b]-indoles, N1-(benzyl)-N2-(phenyl)-N2-(sulfonyl)glycinamides, lipoteichoic acids, CpG DNA, and the PamCSK series of peptides.Figure 1.  In native pathogens, such as the herpes virus, an inter-agonist spacing exists between different immunostimulants. In this study, we probed the immunostimulatory effects of a variety of agonists conjugated at discrete molecular distances.

Covalently coupled immunostimulant heterodimers

248th National Meeting (2014)

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