by Xianglin Huang, Bryan L. Roth Bitopic ligands that engage two distinct binding sites offer exciting opportunities for finely tuned control of G protein-coupled receptor signaling. A recent study in PLOS Biology employed click chemistry to generate novel nanobody-small molecule conjugates and demonstrated their logic-gated activity at co-expressed receptor pairs with improved signaling profiles. Bitopic ligands that engage two distinct binding sites offer exciting opportunities for finely tu