Cell-surface receptors are important hubs for cell signaling.Since membrane-bound proteins have low solubility in aqueous buffer,labeling them using a fluorescent tag on surface of cells to facilitate tracking is particularly worthy.Affinity guided covalent conjugation was recently proven to be an effective method for spontaneous and site-specific covalent labeling of cell-surface receptors.[1] Introducing a biocompatible reaction between thiol and α-chloroacetyl into the biological system converted a noncovalent coiled-coil binding interaction into a covalent conjugation reaction.[1] Besides coiled-coils,here we turned to scaffold domains.