Histone deacetylase Trapoxin

Furumai R, Komatsu Y, Nishino N, Khochbin S, Yoshida M, Horinouchi S (2001) Potent histone deacetylase inhibitors built from trichostatin A and cyclic tetrapeptide antibiotics including trapoxin. Proc Natl Acad Sci U S A 98(l) 87-92... 

KijimaM, YoshidaM, SugitaK, Horinouchi S, BeppuT(1993)Trapoxin, an antitumor cychc tetrapeptide, is an irreversible inhibitor of mammahan histone deacetylase. J Biol Chem 268(30) 22429—22435 Kim A, Dean A (2004) Developmental stage differences in chromatin subdomains of the P-globin locus. Proc Natl Acad Sci USA 101 7028-7033... 

Taunton J, Collins JL, Schreiber SL. (1996) Synthesis of natural and modified trapoxins, useful reagents for exploring histone deacetylase function. JAm Chem Soc 118 10412-10422. 

Jung, M., Hoffmann, K., Brosch, G. and Loidl, P. (1997) Analogues of trichostatin A and trapoxin B as histone deacetylase inhibitors. Bioorganic Medicinal Chemistry Letters, 7, 1655-1658. 

Kijima, M., Yoshida, M., Sugita, K., Horinouchi, S. and Beppu, T. (1993) Trapoxin, an antitumor cyclic tetrapeptide, is an irreversible inhibitor of mammalian histone deacetylase. The Journal of Biological Chemistry, 268, 22429-22435. 

In 1993, Yoshida et al. pubhshed trapoxin (TPX, Fig. 3), a fimgal product, which, in contrast to TSA, is an irreversible inhibitor of mammalian histone deacetylase [38]. When the epoxide moiety is reduced to the corresponding primary alcohol, HDAC inhibiting activity is completely lost. This observation emphasizes the importance of the oxirane ring, which most likely binds irreversibly via ring opening at the activated 2-position to a nucleophihc active site residue. 

Sternson SM, Wong JC, Grozinger CM, Schreiber SL, Synthesis of 7200 small molecules based on a substructural analysis of the histone deacetylase inhibitors trichostatin and trapoxin, Org. Lett., 3 4239-4242, 2001. 

Trapoxins were discovered by Itazaki et al. in 1990, from the flingas Helicoma ambiens RF-1023. These compounds exhibit detransformation activity against v-sis oncogene-transformed NIH3T3 cells. Trapoxin A has no effect on human red blood cells, even at a concentration of 250pg/ml and incubation at 37 °C for 2 days Trapoxins are known to inhibit histone deacetylase (HDACl) activity" and trapoxin B has no effect on the stability of HDAC6-PP1 complexes or on tubulin acetylation ... 

Taunton, J., Collins, J. L., Schreiber, S. L. Synthesis of Natural and Modified Trapoxins, Useful Reagents for Exploring Histone Deacetylase Function. J. Am. Chem. Soc. 1996,118,10412-10422. 

They succeeded in isolating two nuclear proteins (55 and 50kDa) that co-purified with histone deacetylase activity by using trapoxin affinity matrix, which was created by cross-linking K-trap with Affi-GellO (5). Both proteins... 

Chromatin remodeling Trapoxin B Cultured cells Reversal of transformed phenotype histone Histone deacetylases... 

Yoshida M, Horinouchi S, Beppu T. Trichostatin A and trapoxin Novel chemical probes for the role of histone acetylation in chromatin structure and function. Bioessays 1995 17 423-30. Darkin-Rattray SJ, Gurnett AM, Myers RW et al. Apicidin A novel antiprotozoal agent that inhibits parasite histone deacetylase. Proc Natl Acad Sci USA 1996 93 13143-7. 

Trapoxin B 35 Helicoma amhiens [108] Inhibits en2ymatic activity, and histone deacetylase [109] Schreiber et al. [110]... 

Recently, psammaplins were reported as potent histone deacetylase (HDAC) and DNA methyltransferase (DNMT) inhibitors (see Table X) (772). Eleven psammaplins (see Table X), isolated from the sponge Pseudoceratina purpurea, were tested in the histone deacetylase (HDAC) enzyme assay at concentrations ranging from 16 nM to 10 pM, and the data obtained were compared to that of two standards, trichostatin A 300) and trapoxin A 301). There were three psammaplin derivatives whose IC50 values were in a... 

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