Effects of backbone structures and stereospecificities of lipid A-subunit analogues on their biological activities.

  title={Effects of backbone structures and stereospecificities of lipid A-subunit analogues on their biological activities.},
  author={M. Matsuura and Y. Kojima and J. Homma and Y. Kumazawa and A. Yamamoto and M. Kiso and A. Hasegawa},
  journal={Journal of biochemistry},
  volume={99 5},
Among chemically synthesized analogues corresponding to the nonreducing sugar part of lipid A, we have found an analogue (GLA-27) which exhibits Limulus, mitogenic, polyclonal B cell activation (PBA), interferon-inducing, and tumor necrosis factor (TNF)-inducing activities but not pyrogenic activity. The structure of GLA-27 comprises 4-O-phosphono-D-glucosamine with tetradecanoyl and 3-tetradecanoyloxytetradecanoyl (C14-O-(C14] groups as the 3-O- and 2-N-acyl substituents, respectively… Expand
Conjugates of biologically active lipid a-subunit analogs with 3-deoxy-d-manno-2-octulosonic acid (KDO) and its methyl ester
Abstract The previously described, biologically active 4- O -phosphono- d -glucosamine derivatives GLA-27, GLA-47, and GLA-60 (all related to bacterial lipid A) were converted into their respectiveExpand
Synthesis of nonreducing-sugar subunit analogs of bacterial lipid a carrying an amide-group (3R)-3-acyloxytetradecanoyl group
Abstract Two types of optically active, 4- O -phosphono- d -glucosamine derivatives related to the nonreducing-sugar subunit of bacterial lipid A, one being 2-[(3 RExpand
Requirement of a properly acylated beta(1-6)-D-glucosamine disaccharide bisphosphate structure for efficient manifestation of full endotoxic and associated bioactivities of lipid A
Several synthetic acylated glucosamine monophosphates, with structures corresponding to the nonreducing or reducing moiety of the lipid A of the Escherichia coli or Salmonella minnesota type, and aExpand
Structure-activity relationship of chemically synthesized nonreducing parts of lipid A analogs.
It was remarkable that protective activities of the endotoxin such as enhancing nonspecific resistance against microbial infections and antitumor activity are preserved in lipid A-subunit analogs of small molecular weight, which at the same time lose all or most toxic activity. Expand
Effect of stereospecificity of chemically synthesized lipid A‐subunit analogues GLA‐27 and GLA‐40 on the expression of immunopharmacological activities
All of the isomers of chemically synthesized lipid A‐subunit analogues showed remarkable antiviral activity against vaccinia virus. Expand
Nonreducing-Sugar Subunit Analogs of Bacterial Lipid a Carrying the Ester-Bound (3R)-3-(Acyloxy)Tetradecanoyl Group
Abstract In order to elucidate further the relationship between the composition of the fatty acyl groups in the nonreducing-sugar subunit of bacterial lipid A and its biological activity,Expand
Enhancement of nonspecific resistance to viral infection by chemically synthesized lipid A-subunit analogs with different backbone structures and acyl groups.
Protection against vaccinia virus infection and induction of interferon (IFN) were investigated in Propionibacterium acnes-primed mice following treatment with chemically synthesized lipid A-subunit derivatives, and the nature and position of the acyl substituents are important for achieving the antiviral effects. Expand
Enhancement of nonspecific resistance to bacterial infections and tumor regressions by treatment with synthetic lipid A-subunit analogs. Critical role of N- and 3-O-linked acyl groups in 4-O-phosphono-D-glucosamine derivatives.
Enhancement of nonspecific resistance against Pseudomonas aeruginosa infection and regression of growth of Meth A fibrosarcoma by chemically synthesized lipid A-subunit analogs,Expand
Immunostimulatory activity of 1-O-acylated muramyl dipeptides, with or without a 6-O-phosphoryl group, in aqueous form.
Acylated MDP analogs enhanced non-specific resistance against P. aeruginosa infection when the analogs were administered i.p. on the day before the infection and was closely related to the accumulation of polymorphonuclear cells in the peritoneal cavity. Expand
The Chemical Modification of the C-1 Substituent of A 4-O-Phosphono-O-Glucosamine Derivative (GLA-27) Related to Bacterial Lipid A
Abstract 1-Thio and 1-O-phosphono derivatives (9-11 and 15) of 2-deoxy–4-O-phosphono-3-O-tetradecanoyl-2-[(3RS)-3-tetradecanoyloxytetradecan-amido]-D-glucose (GLA-27-RS), which exhibits some of theExpand