Cytotoxic dinorditerpenoids from Drypetes perreticulata.

Four hitherto unknown dinorditerpenoids, dryperreins A-D of the pimarane class, together with eight known triterpenoids, were isolated from twigs and leaves of Drypetes perreticulata. The structures of dryperreins A-D were elucidated on the basis of detailed spectroscopic analysis as (10S)-11,12-dihydroxy-6-methoxy-15,16-dinorpimara-5,8,11,13-tetraene-3,7-dione, (10S)-6,11,12-trihydroxy-15,16-dinorpimara-5,8,11,13-tetraene-3,7-dione, (10S)-11,12-dihydroxy-6-methoxy-15,16-dinorpimara-1,5,8,11,13-pentaene-3,7-dione, and (10S)-6,11,12-trihydroxy-15,16-dinorpimara-1,5,8,11,13-pentaene-3,7-dione, respectively. Dryperreins C and D exhibited strong cytotoxicity in vitro against HL-60 human tumor cell line. The structure-activity relationship of the cytotoxic compounds was briefly discussed.

Chemical constituents from Brucea javanica.

Fourteen apotirucallane-type triterpenoids, named brujavanones A-N, were isolated from the twigs of Brucea javanica, along with four known quassinoids and seven known lignans from the seeds of B. javanica. Their structures were elucidated on the basis of extensive spectroscopic data analysis. The structure of a previously reported triterpenoid, bruceajavanin C, was revised as its C-21 epimer. The cytotoxic activities of triterpenoids and quassinoids against two human tumor cell lines, HL-60 and A-549, were evaluated, but all the compounds were inactive (IC50>10 µM).

Proteomic analysis of differential protein expression in a human hepatoma revertant cell line by using an improved two-dimensional electrophoresis procedure combined with matrix assisted laser desorption/ionization-time of flight-mass spectrometry.

The proteomic profiles of a human hepatoma revertant, CL1, and its original cell line, SMMC7721, were compared by using an improved two-dimensional electrophoresis (2-DE) procedure, with multi-IPGstrips gels (length

Chromatin targeting of de novo DNA methyltransferases by the PWWP domain.

DNA methylation patterns of mammalian genomes are generated in gametogenesis and early embryonic development. Two de novo DNA methyltransferases, Dnmt3a and Dnmt3b, are responsible for the process. Both enzymes contain a long N-terminal regulatory region linked to a conserved C-terminal domain responsible for the catalytic activity. Although a PWWP domain in the N-terminal region has been shown to bind DNA in vitro, it is unclear how the DNA methyltransferases access their substrate in chromatin in vivo. We show here that the two proteins are associated with chromatin including mitotic chromosomes in mammalian cells, and the PWWP domain is essential for the chromatin targeting of the enzymes. The functional significance of PWWP-mediated chromatin targeting is suggested by the fact that a missense mutation in this domain of human DNMT3B causes immunodeficiency, centromeric heterochromatin instability, facial anomalies (ICF) syndrome, which is characterized by loss of methylation in satellite DNA, pericentromeric instability, and immunodeficiency. We demonstrate that the mutant protein completely loses its chromatin targeting capacity. Our data establish the PWWP domain as a novel chromatin/chromosome-targeting module and suggest that the PWWP-mediated chromatin association is essential for the function of the de novo methyltransferases during development.