ml9b00144_si_001.pdf (1.79 MB)
One-step Heck Reaction Generates Nonimmunosuppressive FK506 Analogs for Pharmacological BMP Activation
journal contribution
posted on 2019-08-21, 20:29 authored by Yuefan Wang, Brandon J. Peiffer, Qi Su, Jun O. LiuFKBP12 ligands such as FK506 have
been shown to activate the BMP
signaling pathway and facilitate tissue regeneration. However, the
immunosuppressive activity of FK506 limits its clinical application.
Using Heck reaction, we generated nonimmunosuppressive analogs of
FK506 by fusing heterocycles to the calcineurin (CN) binding domain
of FK506. Structure–activity relationships provided novel mechanistic
insights into the FK506–CN interaction that can be exploited
for rational design of future analogs.