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The Protein Kinase Inhibitor Balanol: Structure – Activity Relationships and Structure-Based Computational Studies

[ Vol. 8 , Issue. 6 ]

Author(s):

Vineet Pande, Maria J. Ramos and Federico Gago   Pages 638 - 645 ( 8 )

Abstract:


Balanol, a fungal metabolite, is a potent ATP-competitive inhibitor of Protein Kinase C (PKC) and Protein Kinase A (PKA), important targets in oncology. Since its discovery in 1993, a number of studies have been performed in order to design selective and bioavailable balanol analogs. Several crystal structures of PKA in complex with balanol and a few analogs bound within the catalytic site have also been solved providing insight about the key interactions for binding. The PKA-balanol complex has also served as an interesting model system for structurebased ligand design and validation of a number of computational methodologies aimed at both understanding the physical basis for molecular recognition and addressing the important issue of protein flexibility in ligand binding. We provide an overview of the structure-activity relationships of balanol analogs and summarize the progress made in structural and computational studies involving balanol.

Keywords:

Balanol, structure activity relationships, kinases, computational chemistry, x-ray crystal structure, protein flexibility, adenosine triphosphate

Affiliation:

Departamento de Farmacologia,Universidad de Alcala, Alcala de Henares, 28871 Madrid, Spain.



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