Skeletal protein protection: the mode of action of an anti-osteoporotic marine alkaloid, norzoanthamine.

Bone is composed of mineralized collagen fibrils. A marine alkaloid, norzoanthamine, accelerates the formation of a collagen-hydroxyapatite composite and enhances collagen release from an immobilized matrix vesicle model. Norzoanthamine recognizes a peptide chain nonspecifically and stabilizes its secondary structure, and collagen has polyvalent binding sites for norzoanthamine. This collagen-norzoanthamine supramolecular association is considered to be one of the most significant modes of action for enhancement of bone formation. The facts that norzoanthamine is nontoxic and that it has a collagen protective activity indicate that it may provide significant therapeutic benefits. In particular, it may be a promising drug candidate for osteoporosis treatment and prevention. Interestingly, norzoanthamine suppressed the proteolysis of not only collagen but also elastin and bovine serum albumin, so it apparently has a universal protective effect of guarding extracellular matrix proteins from degradation. This result suggests that norzoanthamine protect skeletal proteins in the host animal body from external stresses and possibly enhance survival.