Development platforms: Multi-pass transmembrane proteins

Transmembrane proteins involve various physiological functions, including protein ligation, recognition, transport, anchoring, and transduction. Several diseases are connected with abnormalities in the function of transmembrane proteins.

Transmembrane proteins are major drug targets, with around 50% of drugs targeting them. However, their usage in drug development has been limited due to poor expression, unstable purification, in vitro insolubility, and difficulty preserving native conformation.

Sino Biological is dedicated to creating multi-pass transmembrane protein products and has established three platforms to supply vital raw materials for early-stage medication development.

These platforms include virus-like particles (VLP), detergent micelle, and nanodisc. Through these platforms, Sino Biological provides unique services in addition to multipass transmembrane proteins (4 pass: Claudin-6, Claudin-9, Claudin-18.1, Claudin-18.2; 7 pass: GPRC5D, CXCR4, and SSTR2).

Three multi-pass transmembrane protein platforms

Virus-like particles (VLP) platform

Development platforms: Multi-pass transmembrane proteins

Image Credit: Sino Biological Inc.

The VLP platform can project membrane proteins in their natural conformation on the surface of virus-like particles, generating full-length transmembrane proteins well-tailored for immunization and antibody screening.

Sino Biological provides custom services and multi-pass transmembrane proteins generated by the VLP platform.

Detergent micelle platform

Development platforms: Multi-pass transmembrane proteins

Image Credit: Sino Biological Inc.

The detergent technology platform employs a standard membrane protein extraction process to create purer membrane protein products that match the needs of early drug screening.

Sino Biological provides custom services and delivers multi-pass transmembrane proteins created via the detergent platform.

Nanodisc platform

Development platforms: Multi-pass transmembrane proteins

Image Credit: Sino Biological Inc.

When transmembrane proteins bind to phospholipids, they preserve their activity, and the nanodisc platform makes use of this property to produce stable products ideal for immunization and antibody screening.

Sino Biological provides custom services and offers multi-pass transmembrane proteins generated via the Nanodisc platform.

Product list of transmembrane proteins

VLP platform

Source: Sino Biological Inc.

Target Cat# Product Name Product Order
GPRC5D 24447-HNAH Human GPRC5D-VLP (Full Length) Protein Order Now
GPRC5D 24447-HNAH-B Human GPRC5D-VLP (Full Length) Protein, Biotinylated Order Now
GPRC5D 5A4669-M25H Mouse GPRC5D-VLP (Full  Length) Protein (Flag Tag) Order Now
Claudin-18.1 20047-HNAH Human CLDN18.1-VLP (Full  Length) Protein Order Now
Claudin-18.2 30025-HNAH Human CLDN18.2-VLP (Full Length) Protein Order Now
Claudin-6 16658-HNAH Human CLDN6-VLP (Full Length) Protein Order Now
Claudin-6 16658-HNAH1 Human CLDN6-VLP (Full Length) Protein, Fluorescent Order Now
SSTR2 11644-HNAH Human SSTR2A-VLP (Full Length) Protein Order Now
SSTR2 30097-HNAH Human SSTR2B-VLP (Full Length) Protein Order Now
CXCR4 11325-HNAH Human CXCR4-VLP (Full Length) Protein Order Now
CB2 17646-HNAH Human CB2-VLP (Full Length) Protein Order Now

 

Detergent platform

Source: Sino Biological Inc.

Target Cat# Product Name Product Order
GPRC5D 24447-H18H-DD Human GPRC5D-Detergent Protein (His & FLAG Tag) Order Now
Claudin-6 16658-H61H-DD Human CLDN6-Detergent Protein (His & FLAG Tag) Pre-order

Detergent-based Claudin-18.2 and Claudin-9 proteins are coming soon.

Nanodisc platform

Source: Sino Biological Inc.

Target Cat# Product Name Product Order
GPRC5D 24447-H18H-NA Human GPRC5D-Nanodisc Protein (His & FLAG Tag) Order Now
Claudin-6 16658-H61H-NA Human CLDN6-Nanodisc Protein (His & FLAG Tag) Order Now
Claudin-9 21185-H49H-NA-B Human CLDN9-Nanodisc Protein (His & AVI Tag), Biotinylated Order Now

Nanodisc-based Claudin-18.2 protein is currently being developed.

Featured transmembrane proteins

Human GPRC5D-VLP (full length) protein Cat#: 24447-HNAH

High bioactivity

Development platforms: Multi-pass transmembrane proteins

Immobilized Human GPRC5D-VLP (Full Length) Protein at 5 μg/mL (100 μL/well) binds anti-GPRC5D antibody. Image Credit: Sino Biological Inc.

High batch-to-batch consistency

Development platforms: Multi-pass transmembrane proteins

Immobilized Human GPRC5D-VLP (Full Length) Protein at 5 μg/mL (100 μL/well) binds anti-GPRC5D antibody. Image Credit: Sino Biological Inc.

Human GPRC5D-Detergent protein (His and FLAG Tag) Cat#: 24447-H18H-DD

Development platforms: Multi-pass transmembrane proteins

Immobilized Human GPRC5D-Detergent Protein (His & FLAG Tag) at 5 μg/mL (100 μL/well) on Nickel coated plate binds anti-human GPRC5D antibody. Image Credit: Sino Biological Inc.

Development platforms: Multi-pass transmembrane proteins

Loaded anti-GPRC5D antibody on Protein A Biosensor binds Human GPRC5D-Detergent Protein (His & FLAG Tag) with an affinity constant of 58.1 nM as determined in BLI assay (ForteBio Octet Red384). Image Credit: Sino Biological Inc.

Human GPRC5D-Nanodisc protein (His and FLAG Tag) Cat#: 24447-H18H-NA

Development platforms: Multi-pass transmembrane proteins

Immobilized Human GPRC5D-Nanodisc Protein (His & FLAG Tag) at 5 μg/mL (100 μL/well) can bind anti-Human GPRC5D antibody. Image Credit: Sino Biological Inc.

Development platforms: Multi-pass transmembrane proteins

Loaded anti-GPRC5D antibody on Protein A Biosensor binds Human GPRC5D-Nanodisc Protein (His & FLAG Tag) with an affinity constant of 0.782 nM as determined in BLI assay (ForteBio Octet Red384). Image Credit: Sino Biological Inc.

Development platforms: Multi-pass transmembrane proteins

Captured anti-GPRC5D antibody on anti-Human IgG Fc via CM5 Chip binds Human GPRC5D-Nanodisc Protein (His & FLAG Tag) with an affinity constant of 9.609 nM as determined in an SPR assay (Biacore T200). Image Credit: Sino Biological Inc.

Transmembrane protein platform FAQs

How to choose transmembrane protein technology platforms

Different transmembrane protein platforms have distinct benefits and drawbacks that should be carefully addressed based on downstream applications, cost, preparation time, etc.

Indicators

VLP Platform

Detergent Platform

SMA-Nanodisc Platform

ELISA coating Direct coating Direct coating is not feasible Direct coating
Bioactivity Good Great Good
Stability Stable Unstable Stable
Purity Mixture Pure (target protein only) Pure (target protein only)
SPR/BLI Applicable Applicable (solution adjustment) Suitable
Consideration The concentration indicates total protein concentration.
The preparation period is relatively short.
The preparation period is relatively long.
More costly.
The preparation period is relatively long.
More costly.

 

Is HPLC analysis used to characterize the purity of VLP-based membrane proteins?

To determine the size and homogeneity of the VLP particles in the product solution, the HPLC method is used. The purity of the target protein cannot be guaranteed since the proteins produced by the VLP platform comprise additional endogenous proteins in addition to the target protein. Because VLP products are mixtures, existing VLP product tests mainly consist of bioactivity tests, with protein purity acting simply as a reference.

What should be considered when purchasing membrane protein products for immunization and antibody screening?

Each of the three transmembrane protein platforms has distinct characteristics, and the users are free to select them based on their specific requirements. Compared to cell immunization products, the VLP platform’s products are mixtures with a higher abundance of target proteins.

VLP-based products can be used for immunization and antibody screening when alternative platform products are unavailable. The toxicity of the detergent to immunized animals and the possibility of protein denaturation during immunization must be considered in the case of detergent platform products. The SMA-Nanodisc platform products contain many target proteins while retaining an excellent natural conformation, making them ideal for animal vaccination and antibody screening experiments.

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