TY - JOUR
T1 - Novel trisaccharide based phospholipids as immunomodulators
AU - Bonam, Srinivasa Reddy
AU - Bhunia, Debabrata
AU - Muller, Sylviane
AU - Nerella, Sridhar Goud
AU - Alvala, Mallika
AU - Halmuthur Mahabalarao, Sampath Kumar
N1 - Publisher Copyright:
© 2019
PY - 2019/9
Y1 - 2019/9
N2 - A focused library of novel mannosylated glycophospholipids was synthesized employing imidate coupling and H-phosphate phosphorylation methods. All novel glycophospholipids were evaluated for their receptor interactions by molecular docking studies. Docking studies revealed dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) specific interaction of the glycophospholipid ligand P4 acts, which was further confirmed by in vitro DC-SIGN expression on monocyte-derived dendritic cells (MoDCs). Further, in vitro and in vivo immunomodulatory activity among the six compounds (P1-P6) examined, compound P4 displayed good immunopotentiation and adjuvant properties as indicated by the induced cytokine expression and enhanced ovalbumin (OVA) specific antibody (IgG) titers. Phosphatidylinositol mannosides (PIMs) analogues in the present study enforced the immunomodulatory properties, truncating parent PIMs or tailor-made of PIMs may bring the novel efficacious molecules, which will be useful in vaccine preparation against different diseases.
AB - A focused library of novel mannosylated glycophospholipids was synthesized employing imidate coupling and H-phosphate phosphorylation methods. All novel glycophospholipids were evaluated for their receptor interactions by molecular docking studies. Docking studies revealed dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) specific interaction of the glycophospholipid ligand P4 acts, which was further confirmed by in vitro DC-SIGN expression on monocyte-derived dendritic cells (MoDCs). Further, in vitro and in vivo immunomodulatory activity among the six compounds (P1-P6) examined, compound P4 displayed good immunopotentiation and adjuvant properties as indicated by the induced cytokine expression and enhanced ovalbumin (OVA) specific antibody (IgG) titers. Phosphatidylinositol mannosides (PIMs) analogues in the present study enforced the immunomodulatory properties, truncating parent PIMs or tailor-made of PIMs may bring the novel efficacious molecules, which will be useful in vaccine preparation against different diseases.
KW - Adjuvanticity
KW - Glycophospholipids
KW - Immunomodulators
KW - Innate immunity
KW - Mannosyl trisaccharide
KW - Vaccines
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U2 - 10.1016/j.intimp.2019.105684
DO - 10.1016/j.intimp.2019.105684
M3 - Article
C2 - 31200340
AN - SCOPUS:85067032736
SN - 1567-5769
VL - 74
JO - International Immunopharmacology
JF - International Immunopharmacology
M1 - 105684
ER -