143994-68-7Relevant 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.
scheme or table, 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.
CHEMICAL SYNTHESIS OF PHOSPHATIDYLINOSITOL MANNOSIDE GLYCANS FROM MYCOBACTERIUM TUBERCULOSIS
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Page/Page column 31, (2010/06/11)
The efficient synthesis of phosphatidylinositol mono- to hexa-mannoside (PIM1 to PIM6) is reported. The invention relates to these phosphatidylinositol mono- to hexa-mannosides carrying a linker and a reactive functional group, e.g. the sulfhydryl group, a protein, a fluorescent probe, or a solid phase. The invention further relates to vaccines comprising the PIMs linked to a carrier protein or an antigen
Synthesis of mycobacterial triacylated phosphatidylinositol dimannoside containing an acyl lipid chain at 3-O of inositol
Patil, Pratap S.,Hung, Shang-Cheng
supporting information; experimental part, p. 2618 - 2621 (2010/08/22)
A seven-step synthesis of triacylated phosphatidylinositol dimannoside is described from myo-inositol 1,3,5-orthoformate. It proceeded in 31% overall yield via a highly regioselective and stereoselective 2,6-di-O-d-mannosylation as the key step.
Total synthesis of phosphatidylinositol dimannoside: A cell-envelope component of mycobacterium tuberculosis
Patil, Pratap S.,Hung, Shang-Cheng
supporting information; experimental part, p. 1091 - 1094 (2009/09/28)
Synthesis of phosphatidylinositol mannosides (PIM2), a cell-envelope component of mycobacterium tuberculosis, toward the preparation of higher PIMs, lipoarabinomannan (LM), and lipomannan(LAM), by employing the myo-inositol-derived meso-4,6-dio
Chemical synthesis of all phosphatidylinositol mannoside (PIM) glycans from Mycobacterium tuberculosis
Boonyarattanakalin, Siwarutt,Liu, Xinyu,Michieletti, Mario,Lepenies, Bernd,Seeberger, Peter H.
supporting information; experimental part, p. 16791 - 16799 (2009/04/14)
The emergence of multidrug-resistant tuberculosis (TB) and problems with the BCG tuberculosis vaccine to protect humans against TB have prompted investigations into alternative approaches to combat this disease by exploring novel bacterial drug targets and vaccines. Phosphatidylinositol mannosides (PIMs) are biologically important glycoconjugates and represent common essential precursors of more complex mycobacterial cell wall glycolipids including lipomannan (LM), lipoarabinomannan (LAM), and mannan capped lipoarabinomannan (ManLAM). Synthetic PIMs constitute important biochemical tools to elucidate the biosynthesis of this class of molecules, to reveal PIM interactions with host cells, and to investigate the function of PIMs as potential antigens and/or adjuvants for vaccine development. Here, we report the efficient synthesis of all PIMs including phosphatidylinositol (Pl) and phosphatidylinositol mono- to hexa-mannoside (PIM1 to PIM6). Robust synthetic protocols were developed for utilizing bicyclic and tricyclic orthoesters as well as mannosyl phosphates as glycosylating agents. Each synthetic PIM was equipped with a thiol-linker for immobilization on surfaces and carrier proteins for biological and immunological studies. The synthetic PIMs were immobilized on microarray slides to elucidate differences in binding to the dendritic cell specific intercellular adhesion molecule-grabbing nonintegrin (DC-SIGN) receptor. Synthetic PIMs served as immune stimulators during immunization experiments in C57BL/6 mice when coupled to the model antigen keyholelimpet hemocyanin (KLH).
Phosphatidylinositol mannosides: Synthesis and suppression of allergic airway disease
Ainge, Gary D.,Hudson, Jennifer,Larsen, David S.,Painter, Gavin F.,Gill, Gurmit Singh,Harper, Jacquie L.
, p. 5632 - 5642 (2007/10/03)
Phosphatidylinositol mannoside (PIM) extracts from mycobacteria have been shown previously to suppress allergic airway inflammation in mice. To help determine the structural requirements for activity, PIM12 (1), PIM16 (2) and PIM2 (3
Regioselective mannosylation routes to the antigenic myo-inositol component of Mycobacterium tuberculosis
Anilkumar,Gilbert, Mark R.,Fraser-Reid, Bert
, p. 1993 - 1997 (2007/10/03)
A differentially protected derivative of myo-inositol with free hydroxyl groups at C6 and C2 is regioselectively mannosylated at C2, and subsequently at C6 with the same or a different donor to give the dimannosylated inositol antigenic core of Mycobacterium tuberculosis. Deacetylation now frees C1 for phosphorylation. (C) 2000 Elsevier Science Ltd.
