Developing small molecule agonistic ligands for tyrosine kinase receptors has been difficult,
and it is generally thought that such ligands require bivalency. Moreover, multisubunit
receptors are difficult to target, because each subunit contributes to ligand affinity, and each
subunit may have distinct and sometimes opposing functions. Here, the nerve growth factor
receptor subunits p75 and the tyrosine kinase TrkA were studied using artificial ligands that
bind specifically to their extracellular domain. Bivalent TrkA ligands afford robust signals …