New cathepsin D inhibitor library utilizing hydroxyethyl isosteres with cyclic tertiary amines.

The design and synthesis of hydroxyethylamine isosteres as inhibitors of cathepsin D based on SAR data have been accomplished. A library of 96 of these hydroxyethylamine isosteres are described and many have proven to be very potent inhibitors of human cathepsin D activity as measured using a fluorometric assay technique, via peptide substrate Ac-Glu-Glu(Edans)-Lys-Pro-Ile-Cys-Phe-Phe-Arg-Leu-Gly-Lys(Methyl Red)-Glu-NH(2). Compounds showing strongest inhibition of cathepsin D activity were those that contain a hydroxyethyl-N'-2- or N'-(4-chlorophenyl)piperazine moiety (IC(50) values range from 0.

Ultrastructure of neurons and synapses in the tentacle gastrodermis of the sea anemone Calliactis parasitica.

Little is known about gastrodermal neurons and synapses in the tentacles of sea anemones. Using transmission electron microscopy of serial thin sections of Calliactis parasitica, we have identified both a sensory cell and a ganglion cell with granular vesicles originating from the Golgi complex and have identified four types of synapses in the tentacular gastrodermal nerve plexus. The sensory cell has a recessed apical cilium with a basal body and a perpendicularly oriented centriole, below which are several strands of striated rootlets surrounded by mitochondria.