Potent anti-calmodulin activity of cyclotetradepsipeptides isolated from Isaria fumosorosea using a newly designed biosensor

Seven cyclotetradepsipeptides, namely beauverolides C (1), F (2), I (3), Ja (4), L (5), M (6), and N (7), were isolated from the entomopathogenic fungus Isaria fumosorosea. The beauverolides were evaluated as potential Calmodulin (CaM) inhibitors using the newly designed CaM biosensor hCaM M124C-AF350; these peptides displayed high affinity to the protein with dissociation constants (Kd) ranging from 0.078 μM to 3.44 μM. Beauverolide Ja, the only one containing a tryptophan residue in its structure, showed the highest affinity. The docking study predicted that beauverolides could bind to CaM in the same site of interaction as chlorpromazine, a well-known Calmodulin ligand.