No abstract

Peptide deformylase (PDF) has been identified as a promising antibacterial and herbicide target. A structurally novel class of inhibitors containing a 2-thioxo-thiazolidin-4-one heterocycle substituted by an arylidene group at the 5-position and a hexanoic acid side chain at the 3-position was discovered independently via high-throughput screening and virtual ligand screening. Data mining and analogue synthesis established a structure--activity relationship for the side chain region that is consistent with the docked structure.

3 Rat brain membranes were also shown to possess a population of saturable, speci®c [ 3 H]-BIDN binding sites, though of lower a nity than in rootworm and with a di erent pharmacological pro®le. Of the insecticidal GABAergic convulsants that displaced [ 3 H]-BIDN from rootworm, cockroach (Periplaneta americana) and rat brain membranes, many were more e ective in rootworm. 4 Functional GABA-gated chloride channels of rootworm nervous system and of cockroach nerve and muscle were blocked by BIDN, whereas cockroach neuronal GABA B receptors were una ected. 5 Expression in Xenopus oocytes of either rat brain mRNA, or cDNA-derived RNA encoding a GABA receptor subunit (Rdl) that is expressed widely in the nervous system of Drosophila melanogaster resulted in functional, homo-oligomeric GABA receptors that were blocked by BIDN. Thus, BIDN probes a novel site on GABA-gated Cl 7 channels to which a number of insecticidally-active molecules bind.

Received J a n u a r y 23, 1989 Improvements in the chirospecific synthesis of (+)-anatoxin from D-glutamic acid have resulted in a process that gives enantiomerically pure material in reproducible 25 % overall yield. The major synthetic modifications have been in the decarbonylative iminium ion cyclization and in the introduction of the enone moiety. With multigram quantities of (+)-anatoxin thus available, a series of nitrogen and side chain modified analogues has been prepared. These analogues were chosen to provide probes for the agonist-receptor interaction model of acetylcholine. They include secondary, tertiary, and quatemary nitrogen derivatives and those in which the carbonyl function has been converted to secondary and tertiary alcohol and ester functions. Cheng, M. T.; Mutter, L. C.; Abood, L.G. J . Am. Chem. SOC. 1986,108, 7864. (c) Compound (+)-3 is the precursor of (+)-l in Edwards' synthesis of (+)-anatoxin from cocaine;% 3 has also been synthesized in racemic form.