.BETA.-TURN PEPTIDOMIMETIC CYCLIC COMPOUNDS

摘要

Proteolytically stable small molecule .beta.-turn peptidomimetic compounds have been identified as agonists or antagonists of neurotrophin receptors, such as TrkA. A compound of particular interest binds the immunoglobulin-lik e C2 region of the extracellular domain of TrkA, competes the binding of anoth er TrkA ligand, affords selective trophic protection to TrkA-expressing cell lines and neuronal primary cultures, and induces the differentiation of primary neuronal cultures. The small .beta.-turn peptidomimetic compounds of the invention can activate a tyrosine kinase neurotrophin receptor that normally binds a relatively large protein ligand. Such compounds that bind t he extracellular domain of Trk receptors are useful pharmacological agents to address disorders where Trk receptors play a role, by targeting populations selectively.