GPCR SdAb Development Service

One important class of therapeutic targets is represented by G-protein-coupled receptors (GPCRs). The VHH might offer innovative treatments focused on GPCRs. The benefits of small compounds and monoclonal antibodies are combined in antigen-binding fragments of human cytotoxicity antibodies. As treatments, sdAbs are becoming more popular. They are also beginning to be used as high-quality tools in GPCR research as well as diagnostics. To support the investigation of GPCR structure and signaling, Creative Biolabs provides a service for the production of GPCR sdAbs.

Advantages of Nbs in GPCRs

Compared to conventional antibody-based compounds, Nbs' biochemical characteristics offer benefits, which enable a wide range of biotechnological and medicinal applications. Nbs have exceptional biochemical and pharmacological properties, which are mostly attributed to their tiny size, single domain nature, and hydrophilic qualities.
One significant benefit over the high manufacturing costs of mAb-based biologics is the simple and economical synthesis of Nbs. Nbs are produced in a simple manner. Because of its monomeric structure, lack of post-translational modifications, and high-aqueous solubility, Nbs can be produced affordably in a range of cell expression systems, whether they are bacterial, yeast, plant, or mammalian in origin.
Nbs' strong affinity and specificity for their target are among its main advantages. Because of their affinity, which lies in the nanomolar–picomolar range, Nbs are excellent choices for scientific, medical, and diagnostic applications.
Not only can the Nb be used to customize half-life, but it can also be used to boost avidity and produce multispecific Nbs. When two identical or different Nbs that recognize separate epitopes on the same antigen are coupled, dramatic increases in avidity and potency relative to their monovalent counterparts are shown.

Applications of Nbs in GPCRs

Modulation of GPCR function

Chemokine receptors and their ligands were the names of the first Nbs that targeted GPCRs. Nbs against CXCR4 were found by phage display and counterselection after llamas were immunized with intact CXCR4-expressing HEK293T cells using a whole cell vaccination procedure. The extracellular loop 2 (ECL2) is bound by the CXCR4–Nbs with great affinity and specificity, and they thereby potently block CXCL12-induced signaling and chemotaxis. Furthermore, CXCR7–Nbs exhibit strong affinity and antagonistic properties because they can prevent β-arrestin 2 from being recruited to CXCR7 by CXCL12. When taken as a whole, Nbs hold significant promise for both therapeutic applications and deeper characterization of the chemokine receptor system.

Abs hold significant promise for therapeutic applications and characterization. (Mujić-Delić, et al, 2014) Fig.1 Potential therapeutic strategies for targeting of the chemokine system.¹

Research tools targeted GPCR

While Nbs' therapeutic potential has garnered much attention, its application as biomolecular tools in fundamental GPCR research are also gaining traction. Nbs are used as crystallization chaperones in biomolecular research. As so-called "G protein mimetics," these GPCR-targeting Nbs improve agonist affinities, suggesting that they maintain the receptor's active states. The application of GPCR-targeting Nbs as conformation-specific biosensors is a significant advantage in GPCR research. Nbs with fluorescent tags offer a way to follow proteins in living cells with never-before-seen resolution.

The benefits of monoclonal antibodies and small molecules are combined in nbs. As G protein mimics and crystallization chaperones, GPCR-targeting Nbs are essential for obtaining structural details about the active state of GPCRs and for usage as conformation-specific biosensors. Creative Biolabs provides GPCR sdAbs development service since these are superior research instruments, diagnostics, and treatments for GPCR studies. Please contact us for more information.

Reference

Mujić-Delić, Azra, et al. "GPCR-targeting nanobodies: attractive research tools, diagnostics, and therapeutics." Trends in pharmacological sciences 35.5 (2014): 247-255.

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