TRAIL Human (114-281 a.a.), Active
Description
Definition and Overview of TRAIL Human (114-281 a.a.), Active
TRAIL Human (114-281 a.a.), Active, is a recombinant soluble form of TNF-related apoptosis-inducing ligand (TRAIL), a type II transmembrane protein belonging to the tumor necrosis factor (TNF) superfamily. This truncated variant spans amino acids 114–281 of the native human TRAIL protein and is produced in Escherichia coli (E. coli). It retains potent apoptotic activity against transformed and tumor cells while sparing most normal cells .
Critical Features:
-
Stability:
-
Activity Preservation: Avoidance of freeze-thaw cycles and oxidation of Cys230 (critical for receptor binding) .
Mechanism of Action and Biological Activity
TRAIL (114-281 a.a.) binds death receptors DR4 (TRAIL-R1) and DR5 (TRAIL-R2), initiating caspase-8-dependent apoptosis. Its selectivity for tumor cells arises from decoy receptors (TRAIL-R3/R4) and osteoprotegerin (OPG) in normal tissues, which block apoptotic signaling .
Enhancement Strategies:
-
Multimerization: Fusion with trimerization motifs (e.g., isoleucine zipper) increases cytotoxicity by stabilizing the active trimeric form .
-
Hexameric TRAIL: ILz(6):TRAIL (hexamerization motif + 114-281 a.a.) shows 10–100x higher potency than trimeric TRAIL in BJAB lymphoma cells .
Preclinical Anticancer Efficacy
-
In Vitro Cytotoxicity: Induces apoptosis in TRAIL-sensitive lines (e.g., Jurkat, HCT116, MDA-MB-231) .
-
Synergy with Chemotherapy: Combines with DNA-damaging agents to overcome resistance in A549 lung cancer cells .
Engineering for Enhanced Delivery
-
Bacterial Secretion Systems: Recombinant Lactococcus lactis engineered to secrete TRAIL (114-281 a.a.) achieves sustained tumoricidal activity in colorectal cancer models .
-
Nanoparticle Conjugation: Soluble TRAIL fused to nanocarriers mimics membrane-bound TRAIL’s oligomeric potency, improving pharmacokinetics .
Comparative Analysis of TRAIL Variants
Product Specs
Product Science Overview
The recombinant human TRAIL protein, specifically the fragment spanning amino acids 114 to 281, is produced in Escherichia coli. This fragment is a non-glycosylated polypeptide chain containing 168-169 amino acids, with a molecular mass of approximately 19.6 to 21 kDa . The protein is purified using proprietary chromatographic techniques to ensure high purity (>95%) and low endotoxin levels (<0.1 EU/µg) .
TRAIL induces apoptosis by binding to its receptors on the cell surface. It interacts with several receptors, including TRAIL-R1 (DR4) and TRAIL-R2 (DR5), which contain death domains that initiate the apoptotic signaling cascade. Additionally, TRAIL can bind to decoy receptors such as TRAIL-R3 (DcR1) and TRAIL-R4 (DcR2), which do not induce apoptosis but can modulate the activity of TRAIL by competing for binding .
The recombinant TRAIL protein is biologically active and has been shown to induce apoptosis in various cell lines, including U937 cells and thyroid carcinoma lines, at concentrations ranging from 0.5 to 2.0 µg/mL . This activity is crucial for its potential therapeutic applications in cancer treatment, as it can selectively induce cell death in tumor cells while sparing normal cells.
The ability of TRAIL to selectively induce apoptosis in cancer cells has made it a promising candidate for cancer therapy. Research has shown that TRAIL can effectively target and kill a wide range of tumor cells, including those resistant to conventional therapies. Additionally, TRAIL’s interaction with decoy receptors provides a mechanism to fine-tune its apoptotic activity, potentially reducing off-target effects and enhancing its therapeutic efficacy .
