Peroxynitrite (ONOO-), an anion and a potent oxidant, generated by the interaction of nitric oxide (NO) and superoxide is able to induce apoptosis in HL-60 human leukemia cells in a time- and concentration-dependent manner. Characteristic morphology of apoptosis can be observed 3 h after HL-60 cells are exposed to 10 microM ONOO-. Treatment of HL-60 cells with increasing concentrations of ONOO- from 1 to 100 microM confirms the concentration dependence of apoptosis as evidenced by: 1) degradation of nuclear DNA of these cells into integer multiples of approximately 200 base pairs; 2) colorimetric DNA fragmentation assay; and 3) evidence of condensation of chromatin and nuclear fragmentation shown by propidium iodide staining. Under the same conditions, peroxynitrite causes apoptosis in another transformed cell line, U-937 cells, but is ineffective at inducing apoptosis in normal endothelial cells derived from human umbilical cord and normal human peripheral blood mononuclear cells. This direct evidence of peroxynitrite inducing apoptosis implicated a new function of this potent oxidant.

Nitrosation of bovine serum albumin with acidified NaNO 2 was compared to that of carboxymethyl-bovine serum albumin in which the thiol group is covalently blocked. Differential ultraviolet-visible (UV-Vis) spectroscopy and a modified Saville assay indicated that a non-cysteine residue(s) in carboxymethyl-bovine serum albumin was nitrosated. The nitrosated carboxymethylbovine serum albumin exhibited similar vasorelaxation activity as that observed with nitrosated bovine serum albumin. Identification of the nitrosated non-cysteine residue(s) was studied using 16 model dipeptides, each of which contained a glycyl residue and a variable residue. Using photolysis-chemiluminescence analysis, modified Saville assay, differential UV-Vis spectroscopy, and bioassays, L-glycyl-L-tryptophan (Gly-Trp) was found to be the only dipeptide that underwent significant nitrosation under these conditions. Liquid chromatography-UV-Vis spectroscopy-mass spectrometry showed that the NO group was attached to the indole nitrogen of tryptophan. Nitrosated Gly-Trp exhibited dose-dependent vasorelaxation and platelet inhibiting activity with apparent EC 50 values of 1.1 ؎ 0.3 and 3.5 ؎ 0.9 M, respectively. Because N-nitroso-Gly-Trp does not release NO radical via spontaneous homolytic N-NO bond fission nor freely diffuse through cellular membranes, the ability of this compound to induce NO ⅐-like biological effects suggests the existence of a (membraneassociated) transnitrosation system that facilitates delivery of-NO to its specific biologic target(s). The nitrosation reaction introduces the nitroso group (-NO) 1 into an organic molecule, leading to the formation of C-nitroso, N-nitroso, O-nitroso, or S-nitroso derivatives of the parent molecule. Commonly used nitrosating agents include HNO 2 , N 2 O 3 , and N 2 O 4 (for review, see Ref. 1), but NO 2 has also been suggested to be effective in this regard (2). Nitrosation reactions may be relevant to the metabolism and

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An asymmetric total synthesis of Prostaglandin E 1 (5) has with the Corey CBS catalyst gave the ω-side chain 7 with Ͼ96% ee. Conjugate addition using the reaction with been achieved in a two-component coupling process. The chiral hydroxycyclopentenone 6 was readily available from dilithiocyanocuprate followed by mild cleavage of the silyl protective groups and enzymatic hydrolysis of the methyl furan with 96% ee. The key reaction step was a kinetic enzymatic resolution followed by an in situ inversion. A ester 22 gave (-)-PGE 1 5 in high yield. catalytic asymmetric reduction of the γ-iodo vinyl ketone 19