Recombinant proteins and peptides for endotoxin biosensors, endotoxin removal, and anti-microbial and anti-endotoxin therapeutics
US6719973B1 · kind B1 · utility
Assignee
Inventors
Key dates
| Filing date | Jul 26, 2000 |
| Grant date | Apr 13, 2004 |
| Priority date | — |
| Expiry date | Jul 26, 2020 |
Classification
- Technology area (CPC Y)Emerging Cross-Sectional Technologies
- CPC primaryY10T436/25375
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
Recombinant fragments of Factor C are disclosed. These proteins and peptides show great potency in recognizing, binding to, neutralizing and removing endotoxin. These molecules can thus be used for anti-microbial, anti-endotoxin, and anti-sepsis therapy. SSCrFCES is a 38 kDa protein representing the LPS-binding domain of Factor C. The ability of SSCrFCES to bind lipid A was analyzed using an ELISA-based assay as well as surface plasmon resonance. Surface plasmon resonance similarly carried out for SSCrFC-sushi-1,2,3-GFP, SSCrFC-sushi-1GFP, and SSCrFC-sushi-3GFP confirmed their superior affinity for endotoxin. The 50% endotoxin-neutralizing concentration of SSCrFCES against 200 EU of endotoxin is 0.069 &mgr;M, suggesting that SSCrFCES is an effective inhibitor of LAL coagulation cascade. Although partially attenuated by human serum, as low as 1 &mgr;M of SSCrFCES inhibits the LPS-induced secretion of hTNF-&agr; and hIL-8 by THP-1 and human pheripheral blood mononuclear cells with a potency more superior than polymyxin B. SSCrFCES is non-cytotoxic, with a clearance rate of 4.7 ml/minute. The LD90 of SSCrFCES for LPS lethality in mice is achieved at 2 &mgr;M. These results demonstrate…
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