Poster Presentation 8th Modern Solid Phase Peptide Synthesis & Its Applications Symposium 2022

Design, Synthesis and Analysis of BDNF mimetic peptides (#121)

Qingqing Lin 1 , Simon Murray 1 , John Karas 1 , Tony Hughes 2 , Susan Northfield 1
  1. The University of Melbourne, Melbourne, VIC, Australia
  2. Monash University, Parkville, VIC, Australia

In chemical biology research, we need compounds that can selectively target a single receptor type. To study proteins like brain-derived neurotrophic factor (BDNF), it is impractical to use the protein itself. This is primarily because BDNF targets two receptor types. BDNF is a member of the neurotrophin family essential for development of both CNS and PNS. It mediates its cellular effects through the TrkB receptor and the p75 neurotrophin receptor (p75NTR). Actions of BDNF vary vastly depending on the cell types and receptor abundance.

Our lab specialises in developing peptides that mimic specific loops of large proteins. My research involves designing, chemically synthesising, and evaluating peptide mimics of BDNF that selectively target either TrkB or p75NTR. Particular attention has been paid to the chemical synthesis of these peptides, as their synthesis is far from trivial. We have published an original research article on a new approach to synthesise multicyclic peptides, and additional work on synthesising multicyclic peptides has been completed and pending publication. Further, we have explored some of these peptides as tools to study BDNF-mediated pain and evaluated their potential as pro-myelinating compounds for the CNS, demonstrating their utility as chemical biology tools.