Synthesis and Evaluation of a Library of Trifunctional Scaffold-Derived Compounds as Modulators of the Insulin Receptor

• DOI: 10.1021/acscombsci.6b00132
• Publication Date: 2016-11-02T17:54:12Z
• Authors: Benjamin Fabre; Jan Pícha; Václav Vaněk; Irena Selicharová; Martina Chrudinová; Michaela Collinsová; Lenka Žáková; Miloš Buděšínský; Jiří Jiráček
• Keywords: 0301 basic medicine; Azides; Molecular Structure; Reproducibility of Results; Receptor, Insulin; Small Molecule Libraries; 03 medical and health sciences; Combinatorial Chemistry Techniques; Insulin; Chromatography, High Pressure Liquid; Copper; Solid-Phase Synthesis Techniques; Protein Binding

We designed a combinatorial library of trifunctional scaffold-derived compounds, which were derivatized with 30 different in-house-made azides. The compounds proposed to mimic insulin receptor (IR)-binding epitopes in the molecule and bind activate this receptor. This work has enabled us test our synthetic biological methodology prove its robustness reliability for solid-phase synthesis testing libraries compounds. Our effort resulted discovery two able weakly induce autophosphorylation IR at 0.1 mM concentration. Despite these modest results, well document well-known difficulty modulating protein-protein interactions, study represents unique example targeting set nonpeptide that specifically synthesized purpose. believe can open new perspectives development next-generation mimetics based on scaffold structure.