New Templates for Syntheses of Ring-Fused, C10 β-Turn Peptidomimetics Leading to the First Reported Small-Molecule Mimic of Neurotrophin-3
- 21 August 2002
- journal article
- letter
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 45 (20) , 4387-4390
- https://doi.org/10.1021/jm0255421
Abstract
Beta-Turn peptidomimetics 1 were designed to mimic hot spots of neurotrophin-3 (NT-3) and others. Solid-phase syntheses of these were developed, though limitations were encountered with scale-up. Consequently, an alternative design with 2 was investigated. 1 and 2 favored distorted type I beta-turn conformations in solution. It was found that peptidomimetic 2b has NT-3-like neurotrophic activity in cell survival assays, selectively binds the NT-3 receptor TrkC, and induces the tyrosine phosphorylation of the TrkC receptor.Keywords
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