Bivalent peptidomimetic ligands of TrkC are biased agonists and selectively induce neuritogenesis or potentiate neurotrophin-3 trophic signals.

ABSTRACT: This study was initiated to find small molecule ligands that would induce a functional response when docked with neurotrophin Trk receptors. "Minimalist" mimics of beta-turns were designed for this purpose. These mimics are (i) rigid, yet easily folded into turn-like conformations, and (ii) readily accessible from amino acids bearing most of the natural side chains. Gram quantities of 16 of these turn mimics were prepared and then assembled into 152 fluorescein-labeled bivalent peptidomimetics via a solution-phase combinatorial method. Fluorescence-based screening of these molecules using cells transfected with the Trk receptors identified 10 potential ligands of TrkC, the receptor for neurotrophin-3. Analogues of these bivalent peptidomimetics with biotin replacing the fluorescein label w

SUBMITTER: Chen D 

PROVIDER: S-EPMC2756187 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature