Detail of "95991-05-2"

Reference

Immunobiological activities of synthetic lipid A analogs with low endotoxicity

Immunobiological activities of synthetic lipid A analogs with low endotoxicity. Kotani, Shozo; Takada, Haruhiko; Takahashi, Ichiro; Ogawa, Tomohiko; Tsujimoto, Masachika; Shimauchi, Hidetoshi; Ikeda, Takako; Okamura, Haruki; Tamura, Toshihide; et al. (Dent. Sch., Osaka Univ., Suita 565, Japan). Infect. Immun., 54(3), 673-82 (English) 1986. CODEN: INFIBR. ISSN: 0019-9567. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Synthetic lipid-A analogs, b(1-6)glucosamine disaccharide 1,4'-bisphosphates, which possess 4 tetradecanoyl groups at the 2- and 2'-amino, and 3- and 3'-hydroxyl groups (LA-17-PP [100742-63-0]), and 2 (R)-3-hydroxytetradecanoyl and 2 tetradecanoyl groups at the 2- and 2'-amino, and 3- and 3'-hydroxy groups, resp. (LA-18-PP [100742-65-2]), were far less endotoxic than synthetic (LA-15PP (506) [95991-05-2]) and bacterial Escherichia coli-type lipid A's; neither compd. showed any detectable lethal toxicity in chicken embryos or preparatory activity for the local Shwartzman reaction in rabbits. Also both compds. were only weakly pyrogenic and comparably less lethally toxic in galactosamine-loaded mice than the ref. synthetic and bacterial lipid A's and a synthetic counterpart to biosynthetic lipid-A precursor Ia (LA-14PP (406) [91841-27-9]). Nevertheless, LA-17-PP and LA-18-PP exhibited definite in vivo immunoadjuvant activity in mice, and the ability to induce a possible tumor necrosis factor and a/b interferon in Mycobacterium bovis BCG and Propionibacterium acnes-primed mice, resp., although these activities were weaker than those of the ref. lipid A's. The 4'-monophosphate analogs of the above 2 test compds. exhibited neither endotoxic nor beneficial activities, but they showed remarkable in vitro bioactivities comparable to those of the corresponding bisphosphate compds.; the ability to activate the human complement system and the clotting enzyme cascade of horseshoe crab amebocyte lysate, stimulatory effects on guinea pig and murine peritoneal macrophages, and murine splenocytes.

Investigations into the polymorphism of lipid A from lipopolysaccharides of Escherichia coli and Salmonella minnesota by Fourier-transform infrared spectroscopy

Investigations into the polymorphism of lipid A from lipopolysaccharides of Escherichia coli and Salmonella minnesota by Fourier-transform infrared spectroscopy. Naumann, Dieter; Schultz, Christian; Born, Jens; Labischinski, Harald; Brandenburg, Klaus; Von Busse, Gerald; Brade, Helmut; Seydel, Ulrich (Robert Koch-Inst. Bundesgesundheitsamtes, Berlin D-1000/65, Fed. Rep. Ger.). Eur. J. Biochem., 164(1), 159-69 (English) 1987. CODEN: EJBCAI. ISSN: 0014-2956. DOCUMENT TYPE: Journal CA Section: 6 (General Biochemistry) Section cross-reference(s): 26, 75 The polymorphism of lipid A, the endotoxic principle of the lipopolysaccharides of gram-neg. 95991-05-2 and 100742-61-8 are cas registry numbers. These chemicals are also mentioned in this article. bacteria, was investigated in the fully hydrated state of temps. between 5° and 58° via Fourier-transform IR spectroscopy. These measurements were supplemented by x-ray diffraction, fluorescence intensity techniques, and differential thermal anal. Up to 3 distinct phase transitions were detected, with the main transition temps. lying at ~41°, 46°, 44°, and 47° for E. coli lipid A, S minnesota lipid A, and the synthetic lipid A compds. 506 and 516, resp. The 4'-monophosphoryl-lipid A samples exhibited their main transition temps. at considerably higher temps. (~52° for E. coli lipid A). The anal. of CH2 stretching absorption bands as well as the wide-angle scattering behavior of the lipid A samples showed that the main transition apparently involved the completion of hydrocarbon chain melting of lipid A, as typically obsd. for phospholipids. However, the phase transition behavior was much more complex than that usually obsd. for model phospholipid systems. Even below the main transition temp., considerable amts. of the methylene segments of the acyl chain of lipid A assumed gauche conformations. These conformational changes might be related to the occurrence of ￡2 further transitions located at ~22°, 30°, 27°, and 25.5° (first transition) and at ~34°, 42°, 38.5°, and 40.5° (second transition) for E coli lipid A, S. minnesota lipid A, and the synthetic lipid A compds. 506 and 516, resp. Furthermore, by the anal. of some characteristic IR absorption bands related to the hydrophilic backbone, it was demonstrated that the temp.-induced conformational changes occurring within the hydrocarbon chains were constantly and simultaneously accompanied by detectable rearrangements within the interfacial region and the polar head group of lipid A. Up to ~30° the lipid A assemblies were supposed to adopt virtually bilayered, true lamellar arrangements, as revealed by the anal. of CH2 scissoring vibrations and x-ray diffraction pattern. However, as indicated by fluorometric techniques, no stable closed vesicles seemed to be formed even under these conditions. At elevated temps. no straightforward interpretation of the data was possible: although the x-ray data did not indicate any drastic changes in the bilayer arrangement at the mol. level even after completion of the acyl chain melting process, the fluorometric and calorimetric data suggested the existence of more complex supermol. arrangements at temps. above the main transition. .