Search for novel PKC ligands as therapeutic seeds for intractable diseases

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Protein kinase C (PKC) involved in cellular signal transduction is one of the target enzymes fortherapeutics of cancer and Alzheimer’s disease. To explore PKC ligands with novel skeleton, we employed our screening system utilizing synthetic peptides of PKC C1 domains, to succeed to identify several bryostatins, anti-neoplastic marine macrolides, from Japanese bryozoan Bugula neritina. Structure-activity studies of bryostatins 4, 10 and 14 suggested that the ester group at position C20 was not necessary for binding to and activating PKC. Moreover, we screened novel PKC ligands from marine sponges, and found that a marine sponge Theonellasp. contains PKC ligands with high binding affinitycomparable to bryostatins.