Jane E. Dancer

Synthesis of potent inhibitors of histidinol dehydrogenase

Abstract Novel inhibitors of histidinol dehydrogenase are described. The most potent inhibitors, compounds 18 ( F i ∗ = 4.4 nM) and 19 ( K i ∗ = 2.9 nM) exploit a hitherto unreported lipophilic binding pocket adjoining the active site. Preliminary SAR data for this pocket are detailed. The electrophilic ketone 6 designed to bind to an active site nucleophile was a considerably weaker inhibitor (IC 50 ∼20μM).

Effect of thiolactomycin on fatty acid synthesis in peas

Abstract Thiolactomycin inhibited fatty acid synthesis in isolated pea chloroplasts. Using [1- 14 C]acetate as a precursor, an I 50 value of ca 20 μM was obtained for a ( R , S ) mixture of thiolactomycin. The antibiotic inhibited the β-ketoacyl-ACP synthase (condensing enzyme: KAS) and the acetyl-CoA: ACP (ACAT) reactions. An examination of the relative inhibition of the three condensing enzymes revealed that their order of sensitivity to thiolactomycin was KAS II > KAS I > KAS III.