Mempro™ Bcl-2 Inhibitors of Programmed Cell Death Production Using Virus-Like Particles

Creative Biostructure provides custom Mempro™ B-cell lymphoma 2 (Bcl-2) inhibitors of programmed cell death production services using virus-like particles.

Virus-like particles (VLPs) are self-assembling multiprotein structures, which are popularly used in vaccine development. VLPs can simulate the native virus, but are non-infectious owing to lacking any viral genetic information. VLPs derived from the Hepatitis B virus (HBV) and composed of the small HBV derived surface antigen (HBsAg). Virus-like particles carrying conformationally-complex membrane proteins (termed lipoparticles) have been applied for integral membrane protein production. Lipoparticles can incorporate a large variety of membrane proteins, such as G-protein coupled receptors (GPCRs) and ion channels.

Lipoparticles can be applied for a wide range of applications, including:

• Antibody screening;
• Phage and yeast display;
• Immunogens/vaccines production;
• Ligand binding assays;
• Nucleic acids and small molecules delivery.
• Other potential applications

Bcl-2 is a superfamily of transmembrane proteins that function as apoptosis regulators (programmed cell death). The Bcl-2 superfamily share a structural domoin that consists of a hydrophobic helix surrounded by amphipathic helices. It is reproted that the pro-survival Bcl-2-like proteins (Bcl-2, Bcl-xL, Bcl-w, Mcl-1, and A1) bind to and inhibit Bax and Bak, which are the terminal effectors directly mediate mitochondrial outer membrane permeabilization. In addition, Bcl-2 inhibitors of programmed cell death superfamily proteins can interact in an inhibitory manner with BCL-2, BCL-XL, and BCL-w.

Figure 1. The structure of Apoptosis regulator Bcl-2. (OPM database)

Creative Biostructure can provide Bcl-2 inhibitors superfamily proteins in the stable, highly purified and native-conformation state. Lipoparticles can be produced from bacterial cells, yeast cells, insect cells, plant cells and mammalian cells for Bcl-2 inhibitors superfamily protein production. Escherichia coli (E. coli) strains, insect cells and mammalian cells are the most widely employed for VLP production. For instance, we can obtain lipoparticles from mammalian cells by co-expressing the retroviral structural core polyprotein, Gag, along with a desired membrane protein. Gag core proteins self-assemble at the plasma membrane, where they bud off and capture membrane proteins of interest. Due to Bcl-2 inhibitors within lipoparticles are directly derived from the cell membrane without mechanical disruption or detergents, the native structure and orientation of Bcl-2 inhibitors are preserved.

Creative Biostructure can provide other various Mempro™ membrane protein production services. Please feel free to contact us for a detailed quote.

References:
A. Roldão, et al. (2010). Virus-like particles in vaccine development. Expert Rev. Vaccines, 9(10): 1149-1176.
S. Cang, et al. (2015). ABT-199 (venetoclax) and BCL-2 inhibitors in clinical development. J. Hematol. Oncol., 8: 129.
S. Willis, et al. (2008). Virus-like particles as quantitative probes of membrane protein interactions. Biochemistry, 47(27): 6988-6890.