A Biophysical Study of Molecular Interaction of Tucatinib with Bovine Serum Albumin

Author:

Jalan Ankita1ORCID,Moyon N. Shaemningwar1ORCID

Affiliation:

1. Department of Chemistry National Institute of Technology Silchar Cachar, Assam 788010 India

Abstract

AbstractA profound understanding of the binding dynamics of drugs with plasma proteins is highly important as it determines its therapeutical potential. Herein, we have investigated the molecular interaction of Tucatinib (TUC), a novel, primitive and highly selective drug for treatment of HER2+ advanced unresectable breast cancer, with bovine serum albumin (BSA) using multi‐pronged spectroscopic techniques and molecular docking. TUC considerably quenched the intrinsic fluorescence of BSA via static quenching mechanism, and it binds to the hydrophobic cleft of subdomain IIA of BSA with a moderate binding affinity. The thermodynamic analysis revealed the major interplay of van der Waals forces and hydrogen bonding interactions in stabilising the binding. The Förster distance ‘r’ signifies feasible energy transfer between BSA and TUC. The conformational analyses indicate some alterations in the protein secondary structure as a consequence of some changes in the protein polar environment due to complex formation. The experimental results are supported by docking analyses.

Publisher

Wiley

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