Accession Number : ADB169784
Title : Specific Mechanism-Based Glycosidase Inhibitors as Chemoprotectants Against Ricin Toxicity.
Descriptive Note : Final rept. 1 Jun 91-31 Aug 92,
Corporate Author : CREIGHTON UNIV OMAHA NE
Personal Author(s) : Stohs, Sidney J.
Report Date : 15 SEP 1992
Pagination or Media Count : 51
Abstract : Ricin is prototypical of many protein toxins, and is one of the most toxic compounds known to man. At the present time, no specific treatment is available for protein toxin exposure. Recent studies have shown that ricin exhibits a glycosidase activity which specifically removes an adenine base from rRNA, resulting in an inhibition of protein elongation and death of exposed animals. We have synthesized eight potential irreversible glycosidase inhibitors. The eight compounds were synthesized according to published methods, and the purities of the products were determined by melting point determination, elemental analysis, IR spectra, NMR spectra, and mass spectroscopy. Sufficient quantities of each of the eight compounds were synthesized to test their chemoprotectant activity against ricin in two cell lines, namely, a macrophage J744A.1 cell line and a Chinese hamster ovary cell line. The release of lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) were assessed as parameters of cytotoxicity after treatment with ricin or potential chemoprotectants. Alamine aminotransferase (ALT) was shown not to be a useful assay of cytotoxicity.
Descriptors : *GLYCOSIDASES, *RICIN, *TOXICITY, ADENINE, AMINOTRANSFERASES, CELLS(BIOLOGY), DEATH, DEHYDROGENASES, DETERMINATION, ELONGATION, HAMSTERS, INHIBITION, INHIBITORS, LACTATES, MACROPHAGES, MASS SPECTROSCOPY, MELTING POINT, OVARIES, PARAMETERS, PROTEINS, QUANTITY, RELEASE, SPECTRA, SPECTROSCOPY, TEST AND EVALUATION, IN VITRO ANALYSIS, IN VIVO ANALYSIS, ENZYMES, TISSUE CULTURE CELLS, CULTURES(BIOLOGY), RIBONUCLEIC ACIDS.
Subject Categories : Toxicology
Distribution Statement : APPROVED FOR PUBLIC RELEASE