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US 8,940,703 B2Granted
Inhibitors of TLR signaling by targeting TIR domain interfaces
AssigneeUniversity of Maryland, Baltimore
InventorVladimir Toshchakov
Life of this patent
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Abstract
TIR-domain decoy peptides and TIR domain peptides are disclosed, as well as methods of using the peptides in the regulation of toll-like receptor (TLR) activation and signaling.
Claims9
A method of inhibiting TIR:TIR interaction between two TIR (Toll/IL-1 receptor) domain-bearing proteins, comprising contacting a cell expressing TIR domain-bearing proteins with one or more TIR-derived decoy peptides, wherein the TIR-derived decoy peptides are selected from the group consisting of:
- TRAP (Toll/interleukin-1 receptor domain-containing adapter protein) based, TIR-derived decoy peptides
- TR3 (RQIKIWFQNRRMKWKKEGSQASLRCF;
- SEQ ID NO:1),
- TR5 (RQIKIWFQNRRMKWKKELCQALSRSHCR;
- SEQ ID NO:2),
- TR6 (RQIKIWFQNRRMKWKKPGFLRDPWCKYQML;
- SEQ ID NO:3),
- TR9 (RQIKIWFQNRRMKWKKAAYPPELRFMYYVD;
- SEQ ID NO:4),
- TR11 (RQIKIWFQNRRMKWKKGGFYQVKEAVIHY;
- SEQ ID NO:5),
- TRAM (TIR domain-containing adapter-inducing interferon-β-(TRIF-) related adapter molecule) based, TIR-derived decoy peptides
- TM4-ΔC(RQIKIWFQNRRMKWKKIVFAEMPCG;
- SEQ ID NO:7),
- TM6 (RQIKIWFQNRRMKWKKENFLRDTWCNFQFY;
- SEQ ID NO:8),
- TRIF (TIR domain-containing adapter-inducing interferon-β) based, TIR-derived decoy peptides
- TF5 (RQIKIWFQNRRMKWKKCLQDAIDHSGFT;
- SEQ ID NO:10),
- TF5-ΔC(RQIKIWFQNRRMKWKKCLQDAIDHS;
- SEQ ID NO:11), MyD88 based, TIR-derived decoy peptides
- M3 (RQIKIWFQNRRMKWKKEQTDYRLKLC;
- SEQ ID NO:12),
- M5 (RQIKIWFQNRRMKWKKIASELIEKRCRRM;
- SEQ ID NO:14),
- TLR2 (Toll-like receptor 2) based, TIR-derived decoy peptides
- 2R1 (RQIKIWFQNRRMKWKKRKPKKAPCRDVCYD;
- SEQ ID NO:20),
- 2R3 (RQIKIWFQNRRMKWKKENSDPPFKLC;
- SEQ ID NO:21),
- 2R9 (RQIKIWFQNRRMKWKKPQRFCKLRKIMNT;
- SEQ ID NO:22), and
- 2DD-αD (RQIKIWFQNRRMKWKKEPIERKAIPQRFCK;
- SEQ ID NO:24).
31 more elements
Dependencies are inferred from the claim text.