scholarly journals Mini-review: antibody therapeutics targeting G protein-coupled receptors and ion channels

2020 ◽  
Vol 3 (4) ◽  
pp. 257-264
Author(s):  
Catherine J Hutchings
Keyword(s):  
Ion Channels ◽  
Research And Development ◽  
Small Molecules ◽  
G Protein ◽  
Clinical Studies ◽  
G Protein Coupled Receptors ◽  
Protein Targets ◽  
Antibody Therapeutics ◽  
Wide Range ◽  
G Protein Coupled

Abstract Antibodies are now well established as therapeutics with many additional advantages over small molecules and peptides relative to their selectivity, bioavailability, half-life and effector function. Major classes of membrane-associated protein targets include G protein-coupled receptors (GPCRs) and ion channels that are linked to a wide range of disease indications across all therapeutic areas. This mini-review summarizes the antibody target landscape for both GPCRs and ion channels as well as current progress in the respective research and development pipelines with some example case studies highlighted from clinical studies, including those being evaluated for the treatment of symptoms in COVID-19 infection.

Ion channels and G protein-coupled receptors as targets for invertebrate pest control: from past challenges to practical insecticides

2021 ◽  
Author(s):  
Yoshihisa Ozoe
Keyword(s):  
Ion Channels ◽  
G Protein ◽  
Pest Control ◽  
Gaba Receptors ◽  
Chloride Channels ◽  
Structural Changes ◽  
G Protein Coupled Receptors ◽  
Octopamine Receptors ◽  
Sites Of Action ◽  
G Protein Coupled

Abstract In the late 1970s, we discovered that toxic bicyclic phosphates inhibit the generation of miniature inhibitory junction potentials, implying their antagonism of γ-aminobutyric acid (GABA) receptors (GABARs; GABA-gated chloride channels). This unique mode of action provided a strong incentive for our research on GABARs in later years. Furthermore, minor structural changes conferred insect GABAR selectivity to this class of compounds, convincing us of the possibility of GABARs as targets for insecticides. Forty years later, third-generation insecticides acting as allosteric modulator antagonists at a distinctive site of action in insect GABARs were developed. G protein-coupled receptors (GPCRs) are also promising targets for pest control. We characterized phenolamine receptors functionally and pharmacologically. Of the tested receptors, β-adrenergic-like octopamine receptors were revealed to be the most sensitive to the acaricide/insecticide amitraz. Given the presence of multiple sites of action, ion channels and GPCRs remain potential targets for invertebrate pest control.

scholarly journals Assembly of G Protein-Coupled Receptors onto Nanosized Bacterial Magnetic Particles Using Mms16 as an Anchor Molecule

2004 ◽  
Vol 70 (5) ◽  
pp. 2880-2885 ◽  
Author(s):  
Tomoko Yoshino ◽  
Masayoshi Takahashi ◽  
Haruko Takeyama ◽  
Yoshiko Okamura ◽  
Fukuichi Kato ◽  
...  
Keyword(s):  
G Protein ◽  
Magnetic Particles ◽  
Lipid Membrane ◽  
Specific Protein ◽  
G Protein Coupled Receptors ◽  
Native Conformation ◽  
Wide Range ◽  
Bacterial Magnetic Particles ◽  
Magnetospirillum Magneticum ◽  
G Protein Coupled

ABSTRACT G protein-coupled receptors (GPCRs) play a central role in a wide range of biological processes and are prime targets for drug discovery. GPCRs have large hydrophobic domains, and therefore purification of GPCRs from cells is frequently time-consuming and typically results in loss of native conformation. In this work, GPCRs have been successfully assembled into the lipid membrane of nanosized bacterial magnetic particles (BMPs) produced by the magnetic bacterium Magnetospirillum magneticum AMB-1. A BMP-specific protein, Mms16, was used as an anchor molecule, and localization of heterologous Mms16 on BMPs was confirmed by luciferase fusion studies. Stable luminescence was obtained from BMPs bearing Mms16 fused with luciferase at the C-terminal region. D1 dopamine receptor (D1R), a GPCR, was also efficiently assembled onto BMPs by using Mms16 as an anchor molecule. D1R-BMP complexes were simply extracted by magnetic separation from ruptured AMB-1 transformants. After washing, the complexes were ready to use for analysis. This system conveniently refines the native conformation of GPCRs without the need for detergent solubilization, purification, and reconstitution after cell disruption.

scholarly journals Isothermal chemical denaturation to determine binding affinity of small molecules to G-protein coupled receptors

2015 ◽  
Vol 473 ◽  
pp. 41-45 ◽  
Author(s):  
Patrick Ross ◽  
Wilhelm Weihofen ◽  
Fai Siu ◽  
Amy Xie ◽  
Hetal Katakia ◽  
...  
Keyword(s):  
Small Molecules ◽  
G Protein ◽  
Binding Affinity ◽  
G Protein Coupled Receptors ◽  
Chemical Denaturation ◽  
G Protein Coupled

scholarly journals Methods used to study the oligomeric structure of G-protein-coupled receptors

2017 ◽  
Vol 37 (2) ◽  
Author(s):  
Hui Guo ◽  
Su An ◽  
Richard Ward ◽  
Yang Yang ◽  
Ying Liu ◽  
...  
Keyword(s):  
Energy Transfer ◽  
G Protein ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
G Protein Coupled Receptors ◽  
Experimental Techniques ◽  
Distribution Analysis ◽  
Wide Range ◽  
And Function ◽  
G Protein Coupled

G-protein-coupled receptors (GPCRs), which constitute the largest family of cell surface receptors, were originally thought to function as monomers, but are now recognized as being able to act in a wide range of oligomeric states and indeed, it is known that the oligomerization state of a GPCR can modulate its pharmacology and function. A number of experimental techniques have been devised to study GPCR oligomerization including those based upon traditional biochemistry such as blue-native PAGE (BN-PAGE), co-immunoprecipitation (Co-IP) and protein-fragment complementation assays (PCAs), those based upon resonance energy transfer, FRET, time-resolved FRET (TR-FRET), FRET spectrometry and bioluminescence resonance energy transfer (BRET). Those based upon microscopy such as FRAP, total internal reflection fluorescence microscopy (TIRFM), spatial intensity distribution analysis (SpIDA) and various single molecule imaging techniques. Finally with the solution of a growing number of crystal structures, X-ray crystallography must be acknowledged as an important source of discovery in this field. A different, but in many ways complementary approach to the use of more traditional experimental techniques, are those involving computational methods that possess obvious merit in the study of the dynamics of oligomer formation and function. Here, we summarize the latest developments that have been made in the methods used to study GPCR oligomerization and give an overview of their application.

scholarly journals Targeting islet G-protein-coupled receptors for type 2 diabetes therapy

2021 ◽  
Author(s):  
Shanta J. Persaud ◽  
Oladapo E. Olaniru ◽  
Patricio Atanes
Keyword(s):  
Type 2 Diabetes ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Pharmaceutical Companies ◽  
Β Cells ◽  
Diabetes Therapy ◽  
Wide Range ◽  
Mass Expansion ◽  
G Protein Coupled

The majority of people with diabetes have type 2 diabetes (T2D), where hyperglycaemia occurs because the islet β-cells are unable to secrete enough insulin, usually in the context of insulin resistance that arises because of fat mass expansion. There are a range of pharmacotherapies in current use to treat T2D and pharmaceutical companies are actively engaged in the development of novel therapies for better glucose control. Ligands that target G-protein-coupled receptors (GPCRs) are obvious candidates because they are used successfully for a wide range of disorders and GLP-1 receptor agonists, which are a relatively recent class of diabetes therapy, have proved to be very effective in treating T2D. We provide here an overview of current successes, some drawbacks and future possibilities for GPCR-based T2D therapies.

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