Potent Anti-Calmodulin Activity of Cyclotetradepsipeptides Isolated from Isaria fumosorosea Using a Newly Designed piosensor

摘要

Seven cyclotetradepsipeptides, namely beauverolides C (1), F (2), I (3),,L (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-AF(350); these peptides displayed high affinity to the protein with dissociation constants (K-d) ranging from 0.078 mu M to 3.44 mu M. Beauverolide J(a), 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.