A designed peptidomimetic agonistic ligand of TrkA nerve growth factor receptors. Academic Article uri icon

abstract

  • 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 binding of another TrkA agonist, affords selective trophic protection to TrkA-expressing cell lines and neuronal primary cultures, and induces the differentiation of primary neuronal cultures. These results indicate that a small beta-turn peptidomimetic can activate a tyrosine kinase neurotrophin receptor that normally binds a relatively large protein ligand. Agents such as D3 that bind the extracellular domain of Trk receptors will be useful pharmacological agents to address disorders where Trk receptors play a role, by targeting populations selectively.

author list (cited authors)

  • Maliartchouk, S., Feng, Y., Ivanisevic, L., Debeir, T., Cuello, A. C., Burgess, K., & Saragovi, H. U.

citation count

  • 80

publication date

  • February 2000