| Abstract
| - Fibroblast growth factor (FGF-1) lacks a signal sequence and is exported by an unconventionalrelease mechanism. The nonclassical export of FGF-1 has been shown to be inhibited by an anti-allergicand anti-inflammatory drug, amlexanox (AMX). We investigate the molecular mechanism(s) underlyingthe inhibitory action of AMX on the release of FGF-1, using a variety of biophysical techniques includingmultidimensional NMR spectroscopy. AMX binds to FGF-1 and enhances its conformational stability.AMX binds to locations close to Cys30 and sterically blocks Cu2+-induced oxidation, leading to theformation of the homodimer of FGF-1. AMX-induced inhibition of the formation of the FGF-1 homodimeris observed both under cell-free conditions and in living cells. Results of this study suggest a novel approachfor the design of drugs against FGF-1-mediated disorders.
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