Biological activities of chemically synthesized derivatives of lipid A: tetraacetyl-monosaccharides linked to 2,3-acyloxyacylglucosamine-4-phosphate.

The mitogenicity and lethal toxicity of chemically synthesized lipid A analogs, in which 2,3-acyloxyacylglucosamine-4-phosphate (acyl-GlcN-4P) is linked to a tetraacetyl (Ac4)-monosaccharide, i.e., Ac4-glucose (A-211), Ac4-mannose (A-212), Ac4-galactose (A-213) or Ac4-glucosamine (A-214), were compared with those of tetraacetyl-3-deoxy-D-manno-2-octulosonic acid (Ac4-KDO) linked to acyl-GlcN-4P (A-203). All the compounds were capable of increasing incorporation of 3H-thymidine into splenocytes of C57BL/6 mice at doses of 50 and 100 micrograms/ml, but the mitogenic activity of A-203 at these doses seems to be stronger than those of the analogs. Intravenous injection of A-203, A-211, and A-213 did not exhibit lethal toxicity even at a high dose (50 micrograms/mouse) in C57BL/6 mice loaded with D-galactosamine hydrochloride. However, A-212 and A-214 showed lethality at the doses of 10 and 50 micrograms/mouse, respectively. The findings indicate that the biological activity of these compounds is affected by the kind of monosaccharide linked to acyl-GlcN-4P.