Histone deacetylase and microtubules as targets for the synthesis of releasable conjugate compounds.
Design and synthesis of an HDAC inhibitor and its merger with three tubulin binders to create releasable conjugate compounds is described. The biological evaluation includes: (a) in vitro reactivity with glutathione, (b) antiproliferative activity, (c) cell cycle analysis and (d) quantification of protein acetylation. The cellular pharmacology study indicated that the HDAC-inhibitor-drug conjugates retained antimitotic and proapoptotic activity with a reduced potency.
Methionyl tRNA acylated within mitochondria isolated from mouse liver, has been resolved into four species by RPC-5 chromatography. All four elute prior to the three cytoplasmic methionyl tRNA species. Of the four species, two are formylated. These results suggest that iso-accepting species of met-tRNAmet exist in mouse liver mitochondria.