TNF a Mutant Human
(a) Analysis by RP-HPLC.
(b) Analysis by SDS-PAGE.
Description
The TNF-alpha Variant is purified by standard chromatographic techniques.
Product Specs
QLVVPSEGLY LIYSQVLFKG QGCPSTHVLL THTISRIAVS YQTKVNLLSA IKSPCQRETP EGAEAKPWYE PIYLGGVFQL EKGDRLSAEI NRPDYLDFAE SGQVYFGIIAF.
Product Science Overview
The human TNF-α gene is located on chromosome 6p21.3 and spans approximately 3 kilobases. It encodes a 233-amino acid-long type II transmembrane protein that forms stable homotrimers. These trimers are the biologically active form of TNF-α. The primary role of TNF-α is to regulate immune cells, induce apoptosis, inhibit tumorigenesis, and retard the proliferation, angiogenesis, and metastasis of cancer cells .
Recombinant mutant human TNF-α (rmhTNF) is a modified form of the natural TNF-α protein. This modification is achieved through genetic engineering techniques, such as polymerase chain reaction (PCR), to alter the TNF-α gene. The resulting product is a non-glycosylated single chain consisting of 151 amino acids with a molecular weight of approximately 16,598 Da .
One notable mutant is the R31D mutant, which has been engineered to preferentially bind to TNF receptor R1 with greater affinity compared to receptor R2. This selective binding is achieved by replacing the arginine residue at position 31 with aspartic acid. The R31D mutant has shown to have a higher affinity for receptor R1, which is associated with pro-inflammatory and apoptotic signaling, while having reduced binding to receptor R2, which is involved in anti-inflammatory and cell survival signaling .
Recombinant mutant TNF-α has been investigated for its potential therapeutic applications, particularly in cancer treatment. For example, thoracic perfusion of rmhTNF combined with cisplatin has been shown to improve the objective response rate and quality of life in patients with malignant pleural effusion (MPE) caused by lung cancer . This combination therapy has demonstrated efficacy in controlling MPE and alleviating symptoms such as dyspnea and chest pain.
Additionally, TNF-α mutants that selectively bind to specific TNF receptors have been designed to retain anti-tumor activity while reducing systemic toxicity. For instance, human TNF-α mutants that bind to the murine TNF-R55 receptor but not to the mouse TNF-R75 receptor have shown retained anti-tumor activity and reduced systemic toxicity in mice .
