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Computational Analysis and Experimental Testing of the Molecular Mode of Action of Gatastatin and Its Derivatives.

ABSTRACT: Given its critical role in cell mitosis, the tubulin γ chain represents a viable chemotherapeutic target to solve the specificity issues associated with targeting α and β tubulin. Since γ tubulin is overexpressed in glioblastoma multiforme (GBM) and some breast lesions, the glaziovianin A derivative gatastatin, presented as a γ-tubulin-specific inhibitor, could yield a successful therapeutic strategy. The present work aims to identify the binding sites and modes of gatastatin and its derivatives through molecular-docking simulations. Computational binding free energy predictions were compared to experimental microscale thermophoresis assay results. The computational simulations did not reveal a strong preference toward γ tubulin, suggesting that further derivatization may be needed to increase its specificity.

SUBMITTER: Vottero P

PROVIDER: S-EPMC10046562 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Computational Analysis and Experimental Testing of the Molecular Mode of Action of Gatastatin and Its Derivatives.

Vottero Paola P Wang Qian Q Michalak Marek M Aminpour Maral M Tuszynski Jack Adam JA

Cancers 20230310 6

Given its critical role in cell mitosis, the tubulin γ chain represents a viable chemotherapeutic target to solve the specificity issues associated with targeting α and β tubulin. Since γ tubulin is overexpressed in glioblastoma multiforme (GBM) and some breast lesions, the glaziovianin A derivative gatastatin, presented as a γ-tubulin-specific inhibitor, could yield a successful therapeutic strategy. The present work aims to identify the binding sites and modes of gatastatin and its derivatives ...[more]

PMID: 36980600

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