Biological hydroperoxides and singlet molecular oxygen generation.

The decomposition of lipid hydroperoxides (LOOH) into peroxyl radicals is a potential source of singlet molecular oxygen ((1)O(2)) in biological systems. Recently, we have clearly demonstrated the generation of (1)O(2) in the reaction of lipid hydroperoxides with biologically important oxidants such as metal ions, peroxynitrite and hypochlorous acid. The approach used to unequivocally demonstrate the generation of (1)O(2) in these reactions was the use of an isotopic labeled hydroperoxide, the (18)O-labeled linoleic acid hydroperoxide, the detection of labeled compounds by HPLC coupled to tandem mass spectrometry (HPLC-MS/MS) and the direct spectroscopic detection and characterization of (1)O(2) light emission. Using this approach we have observed the formation of (18)O-labeled (1)O(2) by chemical trapping of (1)O(2) with anthracene derivatives and detection of the corresponding labeled endoperoxide by HPLC-MS/MS. The generation of (1)O(2) was also demonstrated by direct spectral characterization of (1)O(2) monomol light emission in the near-infrared region (lambda = 1270 nm). In summary, our studies demonstrated that LOOH can originate (1)O(2). The experimental evidences indicate that (1)O(2) is generated at a yield close to 10% by the Russell mechanism, where a linear tetraoxide intermediate is formed in the combination of two peroxyl radicals. In addition to LOOH, other biological hydroperoxides, including hydroperoxides formed in proteins and nucleic acids, may also participate in reactions leading to the generation (1)O(2). This hypothesis is currently being investigated in our laboratory.

New neolignans from Talauma ovata.

The hexane extract of the bark of Talauma ovata yielded three new natural neolignans, identified as acetyl oleiferin-C (4), acetyl oleiferin-F (7) and acetyl oleiferin-G (8), together with the known compounds dihydroguaiaretic acid (1), austrobailignan-5 (2), oleiferin-C (3), austrobailignan-6 (5) and oleiferin-F (6).

Induction of mitogenesis by synthetic peptides related to the structure of human fibroblast growth factor-1

The synthetic peptide Ac-WFVGLKKNGSSKRGPRT-NH2,related to the human FGF-1 sequence, was shown to be mitogenic upon Balb/c 3T3 fibroblasts in culture (ED50=10-20 muM) and to compete with the growth factor for cellular binding (ID50 = 30-50 muM). The results described suggest that the mitogenic activity of the peptide is dependent on the presence of the residues 122-127 (WFVGLK) in its structure. Also, its affinity for the cellular receptors seems to be dependent on the presence of residues that are important for FGF-heparin binding such as K127, K133 and R137.