PLoS Biology November 25, 2025

Development of bitopic nanobody-ligand conjugates targeting G protein-coupled receptors and exhibiting logic-gated signaling

by Shivani Sachdev, Swarnali Roy, Ross W. Cheloha G protein-coupled receptors (GPCRs) are the largest family of plasma membrane-embedded signaling proteins. These receptors are involved in a wide array of physiological processes, marking them as attractive targets for drug development. Bitopic ligands, which are comprised of a pharmacophore that targets the receptor orthosteric site and a linked moiety that binds to a separate site, have considerable potential for addressing GPCR function. Here