Biological activities of chemically synthesized 2-keto-3-deoxyoctonic acid-(alpha 2----6)-D-glucosamine analogs of lipid A.

The mitogenicity, lethal toxicity, and Shwartzman reaction of three derivatives of chemically synthesized 2-keto-3-deoxyoctonic acid-linked 2,3-diacyloxyacylglucosamine-4-phosphate (KDO-GlcN-4-P) were determined. The compounds, A-301 (with di-3-hexadecanoyloxytetradecanoyl at the C-2 and C-3 positions), A-303 (di-3-tetradecanoyloxytetradecanoyl), and A-305 (3-dodecanoyloxytetradecanoyl and 3-tetradecanoyloxytetradecanoyl), induced a significant incorporation of [3H]thymidine into splenocytes of C57BL/6 mice. The compounds A-301 and A-303 showed lethality at a high dose of 50 micrograms per mouse in C57BL/6 mice sensitized with D-galactosamine, whereas A-305 caused toxicity even at a dose of 10 micrograms per mouse. However, the three compounds did not elicit the local Shwartzman reaction in rabbits. These findings indicate that the addition of 2-keto-3-deoxyoctonic acid enhances the mitogenic activity of 2,3-diacyloxyacylglucosamine-4-phosphate but does not affect the lethal toxicity and the induction of Shwartzman reaction.