Significance: A diverse family of lipid-derived levulinaldehydes, isolevuglandins (isoLGs), is produced by rearrangement of endoperoxide intermediates generated through both cyclooxygenase (COX) and free radicalinduced cyclooxygenation of polyunsaturated fatty acids and their phospholipid esters. The formation and reactions of isoLGs with other biomolecules has been linked to alcoholic liver disease, Alzheimer's disease, age-related macular degeneration, atherosclerosis, cardiac arythmias, cancer, end-stage renal disease, glaucoma, inflammation of allergies and infection, mitochondrial dysfunction, multiple sclerosis, and thrombosis. This review chronicles progress in understanding the chemistry of isoLGs, detecting their production in vivo and understanding their biological consequences. Critical Issues: IsoLGs have never been isolated from biological sources, because they form adducts with primary amino groups of other biomolecules within seconds. Chemical synthesis enabled investigation of isoLG chemistry and detection of isoLG adducts present in vivo. Recent Advances: The first peptide mapping and sequencing of an isoLG-modified protein present in human retina identified the modification of a specific lysyl residue of the sterol C27-hydroxylase Cyp27A1. This residue is preferentially modified by iso [4]LGE 2 in vitro, causing loss of function. Adduction of less than one equivalent of isoLG can induce COX-associated oligomerization of the amyloid peptide Ab 1-42 . Adduction of isoLGE 2 to phosphatidylethanolamines causes gain of function, converting them into proinflammatory isoLGE 2 -PE agonists that foster monocyte adhesion to endothelial cells. Future Directions: Among the remaining questions on the biochemistry of isoLGs are the dependence of biological activity on isoLG isomer structure, the structures and mechanism of isoLG-derived protein-protein and DNA-protein cross-link formation, and its biological consequences.

Isolevuglandins (isoLGs) are stereo and structurally isomeric γ-ketoaldehydes produced through free radical-induced oxidation of arachidonates. Some isoLG isomers are also generated through enzymatic cyclooxygenation. Post-translational modification of proteins by isoLG is associated with loss-of-function, cross-linking and aggregation. We now report that a low level of modification by one or two molecules of isoLG has a profound effect on the activity of a multi subunit protease, calpain-1. Modification of one or two key lysyl residues apparently suffices to abolish catalytic activity. Covalent modification of calpain-1 led to intersubunit cross-linking. Hetero- and homo-oligomers of the catalytic and regulatory subunits of calpain-1 were detected by SDS PAGE with Western blotting. N-Acetyl-glycyl-lysine methyl ester and β-amyloid(11-17) peptide EVHHQKL were used as models for characterizing the cross-linking of protein lysyl residues resulting from adduction of iso[4]LGE2. Aminal, bispyrrole and trispyrrole cross-links of these two peptides were identified and fully characterized by mass spectrometry. Aminal and bispyrrole dimers were both detected. Furthermore, a complex mixture of derivatives of the bispyrrole cross-link containing one or more additional atoms of oxygen was found. Interesting differences are evident in the predominant crosslink type generated in the reaction of iso[4]LGE2 with these peptides. More aminal cross-link versus bispyrrole is formed during reaction of the dipeptide with iso[4]LGE2. In contrast, more bispyrrole versus aminal cross-link is formed during the reaction of EVHHQKL with iso[4]LGE2. It is tempting to speculate that the EVHHQKL peptide-pyrrole modification forms noncovalent aggregates that favor the production of covalent bispyrrole cross-links because β-amyloid(11-17) tends to spontaneously oligomerize.

A series of novel 2-arylphenyl ether-3-(1H-1,2,4-triazol-1-yl)propan-2-ol derivatives were designed and synthesized as candidate fungicides. The new compounds were identified by (1)H NMR spectroscopy and element analysis. Their antifungal activities were evaluated. They exhibited excellent antifungal activities against five common pathogens in comparison with the commercial fungicides tebuconazole and difenoconazole. The antifungal activities of three new triazole alcohol compounds were compared with those of tebuconazole and difenoconazole at a concentration of 1 mug/mL.

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A quantitative structure-activity relationship study of antifungal analogues of 3,4-substituted 5-((1H-1, 2, 4-triazol-1-yl)methyl)-4H-1,2,4-triazole Abstract A series of 5-((1H-1, 2, 4-triazol-1-yl)methyl)-4H-1,2,4-triazole derivatives were prepared and evaluated for their antifungal activities. Quantitative structureactivity relationship studies were performed on these compounds using physicochemical parameters as independent parameters and antifungal activity as a dependent parameter, where antifungal activity correlated best (correlation coefficient r [ 0.8) with physicochemical parameters (Hammett's constants r p , F) and van der Waals volume V 1 . Results are interpreted on the basis of multiple regression and cross-validation methodology. Furthermore, the domain of applicability which indicates the area of reliable predictions is defined.