153053-07-7Relevant academic research and scientific papers
Synthesis and toll-like receptor 4 (TLR4) activity of phosphatidylinositol dimannoside analogues
Ainge, Gary D.,Martin, William John,Compton, Benjamin J.,Hayman, Colin M.,Larsen, David S.,Yoon, Sung-Il,Wilson, Ian A.,Harper, Jacquie L.,Painter, Gavin F.
experimental part, p. 7268 - 7279 (2011/12/21)
A series of five PIM2 analogues were synthesized and tested for their ability to activate primary macrophages and modulate LPS signaling. Structural changes included replacement of the fatty acid esters of the phosphatidyl moiety of PIM2 with the corresponding ether or amide. An AcPIM2 analogue possessing an ether linkage was also prepared. The synthetic methodology utilized an orthogonally protected chiral myo-inositol starting material that was conveniently prepared from myo-inositol in just two steps. Important steps in the synthetic protocols included the regio- and α-selective glycosylation of inositol O-6 and introduction of the phosphodiester utilizing phosphoramidite chemistry. Replacement of the inositol core with a glycerol moiety gave compounds described as phosphatidylglycerol dimannosides (PGM2). Biological testing of these PIM compounds indicated that the agonist activity was TLR4 dependent. An ether linkage increased agonist activity. Removal of the inositol ring enhanced antagonist activity, and the presence of an additional lipid chain enhanced LPS-induced cytokine production in primary macrophages. Furthermore, the interruption of the LPS-induced 2:2 TLR4/MD-2 signaling complex formation by PIM2 represents a previously unidentified mechanism involved in the bioactivity of PIM molecules.
ANALOGUES OF PHOSPHATIDYLINOSITOL MANNOSIDES
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Page/Page column 30-31, (2008/12/06)
The invention relates to compounds which are immunomodulatory compounds and, in particular, can induce IL-12 secretion. The invention also relates to compositions containing the compounds, precursors, and prodrugs of these compounds, use of these compounds as adjuvants in combination with vaccines, and use of these compounds for treatment of diseases or conditions relating to infection, atopic disorders, or cancer.
Small angle X-ray scattering (SAXS) and differential scanning calorimetry (DSC) studies of amide phospholipids
Zhai, Xiuhong,Bartel, Markus,Brezesinski, Gerald,Rattay, Bernd,M?hwald, Helmuth,Li, Junbai
, p. 79 - 88 (2007/10/03)
Varying chemically the structure of phospholipids in the region between hydrophobic and hydrophilic segments is expected to have a strong influence on the interaction with water and the phase behavior. This is studied in this work with the motivation to investigate these lipids as potential inhibitors of phospholipase A2. Thus the amide phospholipids l-ether-amide-PC (1-O-hexadecyl-2-N-palmitoyl-2-amino-2-deoxy-sn-glycero-3-phosphocholine), l-ester-amide-PC (1-palmitoyl-2-N-palmitoyl-2-amino-2-deoxy-sn-glycero-3- phosphocholine) and l-ether-amide-PE (1-O-hexadecyl-2-N-palmitoyl-2-deoxy-sn- glycero-3-phosphoethanolamine) have been synthesized and characterized. The phase behavior and thermal transitions in buffer dispersions are examined by a combination of high-sensitivity differential scanning calorimetry (DSC) and small angle X-ray scattering (SAXS) experiments between 10 and 80°C at pH 8.9. The onset temperatures determined from DSC measurements agree well with the starting temperatures of changes in the repeat distance obtained by SAXS measurements. The phases observed are lamellar both below and above the main phase transition. The phase transition temperatures and enthalpies depend strongly on the substitutions in sn-1 position and head group structure. The lamellar repeat distance in gel and liquid-crystalline phases increases with increasing temperature for l-ester-amide-PC and l-ether-amide-PC, whereas the temperature dependence is opposite for the l-ether-amide-PE. The observed behavior is discussed and compared with that of DPPC and DPPE, indicating the strong dependence of hydration and phase behavior on head group structure.
