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Introduction | The clinical use of the potent anti-tumor activity of TNF-a has been limited by the proinflammatory side effects including fever, dose-limiting hypotension, 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 murine TNF-R55 but not to the mouse TNF-R75, exhibits retained anti-tumor activity and reduced systemic toxicity in mice compared with murine TNF-a, which binds to both murine TNF receptors. Based on these results, many TNF-? mutants that selectively bind to TNF-R55 have been designed. These mutants displayed cytotoxic activities on tumor cell lines in vitro, and exhibited lower systemic toxicity in vivo. Recombinant Human TNF-a Variant/Mutant compared with the wild-type, has an amino acid sequence deletion from a.a. 1-7, and the following a.a. substitutes Arg8, Lys9, Arg10 and Phe157 which is proven tohave more activity and with less inflammatory side effect in vivo. |
Synonyms | TNF-alpha, Tumor necrosis factor ligand superfamily member 2, TNF-a, Cachectin, DIF, TNFA, TNFSF2. |
Source | Escherichia Coli. |
Physical Appearance | Sterile Filtered White lyophilized (freeze-dried) powder. |
Formulation | The protein was lyophilized after extensive dialysis against 0.5x PBS pH -7. |
Solubility | It is recommended to reconstitute the lyophilized Tumor Necrosis Factor-alpha Variant in sterile 18MΩ-cm H2O not less than 100µg/ml, which can then be further diluted to other aqueous solutions. |
Stability | Lyophilized Tumor Necrosis Factor-a Variant althoµgh stable at room temperature for 3 weeks, should be stored desiccated below -18°C. Upon reconstitution TNF-a Variant should be stored at 4°C between 2-7 days and for future use below -18°C.For long term storage it is recommended to add a carrier protein (0.1% HSA or BSA).Please prevent freeze-thaw cycles. |
Amino Acid Sequence | MRKRKPVAHV VANPQAEGQL QWLNRRANAL LANGVELRDNQLVVPSEGLY LIYSQVLFKG QGCPSTHVLL THTISRIAVS YQTKVNLLSA IKSPCQRETP EGAEAKPWYE PIYLGGVFQL EKGDRLSAEI NRPDYLDFAE SGQVYFGIIAF. |
Purity | Greater than 95.0% as determined by:(a) Analysis by RP-HPLC.(b) Analysis by SDS-PAGE. |
Biological Activity | The ED50 as determined by the cytolysis of murine L929 cells in the presence of Actinomycin D is < 0.05ng/ml, corresponding to a Specific Activity of 20,000,000 units/mg. |
Usage | NeoScientific's products are furnished for LABORATORY RESEARCH USE ONLY. The product may not be used as drµgs, agricultural or pesticidal products, food additives or household chemicals. |
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