A specific inhibitor of protein tyrosine phosphatase (PTPase), RK-682 (3-bexadecanoyl-5-hydroxymethyl-tetronic acid) was isolated from microbial metabolites. In vitro, RK-682 inhibited dephosphorylation activity of CD45 and VHR with ICso 54 and 2.0 pM, respectively. In situ, sodium orthovanadate and RK-682 enhanced the phosphotyrosine level of Ball-1 cells, a human B cell leukemia, but not the phosphoserinelthreonine level. The PTPase inhibitors, however, had the different arrest point on the cell cycle progression. Sodium orthovanadate inhibited the cell cycle progression at G2/M boundary phase, on the other hand, RK-682 inhibited the GJS transition.
Stevastelin B is a novel immunosuppressant. It inhibited IL-2 or IL-6 dependent gene expression but did not inhibit the phosphatase activity of calcineurin. The structure-activity relationships show that the acidic functional group on the threonine residue and the stearic acid moiety in the stevastelin molecule are important for inhibitory effects on the dephosphorylation activity of VHR in vitro. Stevastelin B might be sulphonylated or phosphorylated after incorporation into the target cell, and then it interacts with protein tyrosine phosphatases and regulates cell-cycle progression.
Six new cembranoid diterpenes, sinulariols C and D (1 and 2a), sinularial A (3), sinularic acid A (4), and sinularones A and B (5 and 6) were isolated from the lipid extract of the soft coral Sinularia mayi, together with four known compounds. The structures of the new compounds were elucidated by means of spectroscopic analyses, Horeau determination, and chemical conversion. Sinulariol C (1) was found to be an C-14 isomer of "13-hydroxyneocembrene" (8a) and gave sinularone A (5) on oxidation. Sinularial A (3) is the first example of a cembranoid aldehyde isolated from marine sources. Compounds 1 to 4 are plausible precursors to the cembranoid lactones found in various soft corals.
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