Recombinant Human TNF-alpha mutant

Biomolecules

TNF is secreted by macrophages, monocytes, neutrophils, T-cells, NK-cells following their stimulation by bacterial LPS. Cells expressing CD4 secrete TNF-alpha while CD8 cells secrete little or no TNF-alpha. The synthesis of TNF-alpha is induced by many different stimuli including interferons, IL-2, GM-CSF. The clinical use of the potent anti-tumor activity of TNF-alfa has been limited by the proinflammatory side effects including fever, dose-limiting hypo tension, hepatotoxicity, intravascular thrombosis, and hemorrhage. Designing clinically applicable TNF-a mutants with low systemic toxicity has been an intense pharmacological interest. Human TNF-a, which binds to the mouse TNF-R55 but not to the mouse TNF-R75, exhibits retained anti-tumor activity and reduced systemic toxicity in mice compared with mouse TNF-a, which binds to both mouse TNF receptors. Based on these results, many TNF-a mutants that selectively bind to TNF-R 55 have been designed. These mutants displayed cytotoxic activities on tumor cell lines, in vitro , and exhibited lower systemic toxicity, in vivo . Recombinant Human TNF-alfa Variant/Mutant compared with the wildtype, has an amino acid sequence deletion from a.a. 1-7, and the following a.a. substitutes Arg 8, Lys 9, Arg 10 and Phe 157 which is proven to have more activity and with less inflammatory side effect, in vivo . Recombinant Human TNF-a Variant produced in, E. coli, is a single, non-glycosylated, polypeptide chain containing 151 amino acids and having a MW = 16.598 kDa. The Human TNF-alpha Variant is purified by standard chromatographic techniques.

Centrifuge vial prior to opening . It is recommended to reconstitute the lyophilized Recombinant Human TNF-alpha Variant in sterile distilled H2O not less than 100 ug/ml, which can then be further diluted to other aqueous solutions.

Less than 0.1 ng/ug (1 EU/ug) of Human TNF-alpha.