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.
Kinugawa
Masaru
M
Department of Chemistry, School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Fukuzawa
Seketsu
S
Tachibana
Kazuo
K
D000469:Alkaline Phosphatase / Q000378:metabolism; D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001381:Azepines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D003094:Collagen / Q000378:metabolism; D017886:Durapatite / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D009391:Nephelometry and Turbidimetry; D010024:Osteoporosis / Q000188:drug therapy*; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D011480:Protease Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011506:Proteins / Q000378:metabolism*; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D013056:Spectrophotometry, Ultraviolet; D014357:Trypsin / Q000378:metabolism
D000470:Alkaloids; D001381:Azepines; D006576:Heterocyclic Compounds, 4 or More Rings; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D011506:Proteins; D011804:Quinolines; C400280:norzoanthamine; D003094:Collagen; D017886:Durapatite; D000469:Alkaline Phosphatase; D010196:Pancreatic Elastase; D014357:Trypsin; D016650:Fluorescein-5-isothiocyanate