MEDI 107 |
| Oligodeoxynucleotide (ODN)-based agonists of TLR9 with two 5'-ends have shown potent immune stimulatory activity compared with agonists that have single 5'-end in mouse and human cell-based assays and in vivo in mice and non-human primates. In the present study, we have designed and synthesized novel linear (C5), and cyclic (C6) linkers (Fig). These novel linkers allowed us to synthesize synthetic agonists of TLR9 with different spatial orientations of the two 5'-ends to understand ODN-receptor interactions and subsequent immune stimulatory profiles. The agonists of TLR9 with new linker modifications maintained immune stimulatory activity in HEK293 cells expressing TLR9, and mouse and human cell-based assays. Additionally, TLR9 agonists with novel linkers induced IL-12 secretion in vivo in mice. These in vitro and in vivo results suggest that TLR9 recognizes synthetic agonists containing new linkers and induces potent immune responses.
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Poster Session
7:00 PM-9:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Medicinal Chemistry |
