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要旨

The secretory peptides luteinizing hormone-releasing hormone, enkephalin, angiotensin, and oxytocin are biochemical antioxidants in aqueous medium. These hormones scavenge free peroxyl radicals, prevent the oxidation of low-density lipoprotein, and inhibit lipid peroxidation in brain membranes. Their capacity to directly suppress free radical-mediated reactions is demonstrated by electron-spin resonance spectroscopy. Electrospray ionization-mass spectrometry analysis of the free radical-quenching reaction reveals distinct oxidation products, including peptide dimers. Moreover, secretory peptide hormones can scavenge reactive nitrogen species derived from nitric oxide and peroxynitrite. An analysis of the structure-activity relationship indicates that their antioxidant activity is derived from the occurrence of solvent-exposed tyrosine and tryptophan residues, which is consistent with the mass spectrometry results. Significant effects in vitro can be observed at nanomolar concentrations, which makes these peptides comparable in potency with classic antioxidants having low molecular mass. Secretory peptide hormones may constitute an important part of the antioxidant defense system, and the sequences of the described antioxidant peptides may be unique lead structures for the rational design of novel antioxidant drugs having an improved pharmacological profil