Disease relevance of chlamydocin

• We show here that these compounds have reciprocal biological activity; HC-toxin is cytostatic against cultured mastocytoma cells, and chlamydocin has host-specific toxin activity against maize [1].

High impact information on chlamydocin

• Chlamydocin, a related cyclic tetrapeptide, also inhibited HD activity [2].
• The maleoyl cyclic tetrapeptide 5 did not inhibit [3H]thymidine incorporation into calf thymus lymphocytes at concentrations 1000-fold higher than the IC50 for chlamydocin (6 nM) [3].
• The synthesis of analogues of the cytostatic cyclic tetrapeptide chlamydocin is described. cyclo(Gly-L-Phe-D-Pro-N beta-Boc-L-Dap) (4) was prepared from N beta-(tert-butyloxycarbonyl)-L-diaminopropionic acid methyl ester (Dap) and Cbz-Gly-L-Phe-D-Pro using DCC/HOBt as the coupling reagent [3].
• Here we show that chlamydocin is a highly potent histone deacetylase (HDAC) inhibitor, inhibiting HDAC activity in vitro with an IC(50) of 1.3 nM [4].
• Although our data indicate a potential link between degradation of survivin and activation of the apoptotic pathway induced by HDAC inhibitors, stable overexpression of survivin does not suppress the activation of caspase-3 or cleavage of p21(cip1/waf1) induced by chlamydocin treatment [4].

Biological context of chlamydocin

• Inhibition of histone deacetylases by chlamydocin induces apoptosis and proteasome-mediated degradation of survivin [4].
• The naturally occurring cyclic tetrapeptide chlamydocin is a very potent inhibitor of cell proliferation [4].

Associations of chlamydocin with other chemical compounds

• HDAC inhibitors such as trichostatin A, trapoxin and chlamydocin could be useful tools to modulate these cellular processes [5].

Gene context of chlamydocin

• We replaced the epoxyketone moiety of chlamydocin with hydroxamic acid to design potent and reversible inhibitors of HDAC [6].

Analytical, diagnostic and therapeutic context of chlamydocin

• We have carried out circular dichroism and molecular modeling studies on chlamydocin-hydroxamic acid analogue and compared it with the solution structure of chlamydocin [6].

References