A peptidomimetic of NT-3 acts as a TrkC antagonist Academic Article uri icon

abstract

  • Neurotrophins are a family of growth factors that regulate the peripheral and central nervous system. We designed and tested a mini-library of small molecules peptidomimetics based on beta-turns of the neurotrophin growth factor polypeptides NT-3, which is the natural ligand for TrkC receptors. Biological studies identified a peptidomimetic 2Cl that exhibited selective antagonism of TrkC. 2Cl reduces TrkC activation and signaling promoted by NT-3, and selectively blocks ligand-dependent cell survival. 2Cl also blocks ligand-independent TrkC activation and signals that take place when the receptor is over-expressed. This work adds to our understanding of how the neurotrophins function through Trk receptors, and demonstrates that peptidomimetics can be designed to selectively disturb neurotrophin-receptor interactions, and receptor activation.

altmetric score

  • 9

author list (cited authors)

  • Brahimi, F., Malakhov, A., Lee, H. B., Pattarawarapan, M., Ivanisevic, L., Burgess, K., & Saragovi, H. U.

citation count

  • 15

publication date

  • July 2009