Synthesis and TGF-β receptor binding inhibition of multibranched compounds

As a part of our project aiming at the discovery of novel synthetic ligands of Transforming Growth Factor Beta (TGF-beta) receptors, five libraries were sequentially synthesised and screened. The biological mechanism involved in the TGF-beta signal transduction proceeds through the hetero-oligomerisation of two TGF-beta subreceptor dimers, Transforming growth factor Beta Receptors (T beta R)-I and II. We hypothesised that synthetic dimers and multibranched-molecules could mimic the natural hormone action by closing the receptor subunits. Mimotope multipin technology was used to synthesise libraries of dimers and tetramers on solid support. This strategy led to the discovery of one of the most potent TGF-beta receptor ligand on type II TGF-beta receptor, described in the literature today.