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Nanobody tethering to dissect GPCR pharmacology
Friday, 09/17/ 2021 @ 4:00 PM - EST
- Dr. Ross Cheloha -
- National Institute of Health -
- Bethesda, MD, USA -
Abstract
Antibodies are powerful and widely used tools for studying basic biological processes and as therapeutic agents; however, their application to addressing GPCR signaling questions poses challenges. Here we use specialized single-domain antibody fragments (nanobodies) in combination with chemical approaches to create conjugates of ligands and antibodies for membrane proteins (CLAMPs). CLAMPs offer advantages over either antibodies or ligands alone. We develop CLAMPs that exhibit tight binding, high receptor subtype selectivity, and potent agonist. We further apply CLAMPs as tools to dissect GPCR signaling. This approach offers expansive possibilities creating pharmacological probes with interesting and useful properties.
About Dr. Ross Cheloha
Ross Cheloha completed his Ph.D. in chemistry at the University of Wisconsin-Madison in the lab of Sam Gellman studying the biological properties of polypeptides that contain amino acids with modified backbone structures. He conducted postdoctoral studies in the lab of Hidde Ploegh at Whitehead Institute at MIT and Boston Children’s Hospital on the use of nanobodies to study cell biology. He opened his independent laboratory at the National Institutes of Health (NIDDK) in the Laboratory of Bioorganic Chemistry in late 2020 where he is developing new tools to assess G protein-coupled receptor function.
Author list and affiliations
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Shivani Sachdev. NIDDK/NIH
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Chino Cabalteja. NIDDK/NIH
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Thomas J. Gardella. Massachusetts General Hospital
Dr. Ross Cheloha on the web
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