| Research Abstract |
In the course of our investigation on the relationship between the immunoadjuvant activity and the structure of the carbohydrate moiety in N-acetylmuramoyl-L-alanyl-D-isoglutamine, which is the minimal, immunoadjuvant-active componentob bacterial cell-wall peptidoglycan, we have established that not only is restricted configuration of the sugar moiety important but also that chemical modifications of the functional groups in the carbohydrate moiety produce, various, important effects on the manifestation of activity. Furthermore, it has been shown that lipophilic derivatives of MDP bearing the lipid moiety at C-1, C-6, or C-1 and C-6 of the sugar skeleton, or at the end of the peptide chain, have strong antitumor and anti-infection activities that are not found MDP itself. On the studies of the relationship between the molecular structure and the biological activity of lipid A, which has been proved to be the active center of the biological activities of bacterial endotoxin, we also have established that several kinds of the activities can be expressed by the nonreducing-sugar subunit analogs of lipid A, and lethal toxicity and pyrogenic activity are about three orders of magnitude weaker than those of lipid A. On the synthetic studies of ganglioside, we have developed the following methods: 1. a stereoselective and high yield synthesis of <alpha>-glycosides of 2-thio-N-acetylneuraminic acid, 2. Synthesis of a suitably, protected N-acetylneuraminic acid, and the analogs, 3. a new glycosidation of sialic acid.
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