A designed peptidomimetic agonistic ligand of TrkA nerve growth factor receptors

A proteolytically stable small molecule beta-turn peptidomimetic, termed D3 , was identified as an agonist of the TrkA neurotrophin receptor. D3 binds the Ig-like C2 region of the extracellular domain of TrkA, competes the bin ding of another TrkA agonist, affords selective trophic protection to TrkA- expressing cell lines and neuronal primary cultures, and induces the differ entiation of primary neuronal cultures. These results indicate that a small beta-turn peptidomimetic can activate a tyrosine kinase neurotrophin recep tor that normally binds a relatively large protein ligand. Agents such as D 3 that bind the extracellular domain of Trk receptors will be useful pharma cological agents to address disorders where Trk receptors play a role, by t argeting populations selectively.