BIOLOGICAL-ACTIVITY OF CHEMICALLY SYNTHESIZED CORE SUGAR LINKED LIPID A ANALOG, HEPTOSE-(ALPHA-1-]5)-2-KETO-3-DEOXYOCTONIC ACID-(ALPHA-2-]6)-2,3-DIACYLOXYACYLGLUCOSAMINE-4-PHOSPHATE

The mitogenicity, lethal toxicity and antitumor activity against Meth A fibrosarcoma and the induction of tumor necrosis factor (TNF) of chemically synthesized compounds designated as A-103, 2,3-diacyloxyacylglucosamine-4-phosphate (G1cN-4-P), and A-503, heptose-(alpha 1 --> 5)-2-keto-3-deoxyoctonic acid (KDO)-linked GlcN-4-P (A-103), were determined. Compound A-103 induced significant incorporation of [H-3]thymidine into splenocytes of C57BL/6 mice at 25-100-mu-g/ml, and A-503 showed the highest incorporation of [H-3]thymidine at 100-mu-g/ml. The mitogenicity of A-503 exhibited a lower activity than of A-103. Compound A-503 showed no lethality at high doses of 25 and 50-mu-g/mouse in C57BL/6 mice loaded with D-galactosamine, whereas A-103 caused the death of one of three mice at a dose of 50-mu-g/mouse. Although, the two compounds with or without muramyl dipeptide showed weak antitumor activity against Meth A fibrosarcoma in BALB/c mice, but there were no remarkable differences between the compounds on antitumor activity. Peritoneal macrophages, stimulated with A-103 or A-503 caused no production of TNF which induces L929 cell lysis in vitro. These findings indicate that the addition of heptose and KDO to GlcN-4-P seems not to affect mitogenic activity, lethal toxicity, antitumor activity and TNF-production of the GlcN-4-P compound (A-103).