Synthesis of a IAP antagonist analogue and its binding investigation with BSA/HSA

The development of new drugs especially novel anti-cancer drugs has become a hot-spot issue that catches scholars' attention in every field. Here a IAP antagonist analogue (IAPA) was synthesized and characterized by NMR and HRMS spectra. Its interaction with proteins, including bovine serum albumin (BSA) and human serum albumin (HSA), were investigated by spectral methods and molecular simulation. Fluorescence quenching, together with UV absorption spectrum and time-resolved fluorescence spectrums indicated a static process in BSA/HSA-IAPA system. Thermodynamic parameters including Delta H and Delta S calculated by Vant't Hoffequation were all positive, showing that hydrophobic force was the major force in the interaction of compound IAPA and BSA/HSA. Site marker competitive displacement experiments proved that IAPA bound to site I at BSA/HSA. Synchronous fluorescence spectrum and three-dimensional fluorescence spectrum were also used to investigate the conformational changes of BSA/HSA after binding with compound IAPA. The above results were further verified by molecular docking. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

The synthesis and characterization of an IAP antagonist analogue (IAPA) and its interaction with proteins were studied in this research. The results showed that the binding between IAPA and proteins occurred through a static process driven by hydrophobic force, specifically at site I of the proteins. Fluorescence spectroscopy and molecular docking were used to further validate the findings.