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

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.

authors

• Burgess, Kevin

published proceedings

• Peptides

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

• 16

complete list of authors

• Brahimi, Fouad||Malakhov, Andrey||Lee, Hong Boon||Pattarawarapan, Mookda||Ivanisevic, Lubijca||Burgess, Kevin||Saragovi, H Uri

publication date

• October 2009

publisher

• Elsevier  Publisher

published in

• Peptides  Journal

keywords

• Animals
• Cell Survival
• Mice
• Molecular Mimicry
• Molecular Structure
• NIH 3T3 Cells
• Neurotrophin 3
• Peptides
• Receptor, IGF Type 1
• Receptor, TrkA
• Receptor, Trkc
• Signal Transduction

PubMed Central ID

• 19647025

Digital Object Identifier (DOI)

• 10.1016/j.peptides.2009.07.015

start page

• 1833

end page

• 1839

volume

• 30

issue

• 10

URL

• http://dx.doi.org/10.1016/j.peptides.2009.07.015