Synthesis of a lipid conjugate of SO3Le(a) and its enhancement on liposomal binding to activated platelets.
3'-O-Sulfated Le(a) (SO3Le(a)) is one of the most potent natural oligosaccharide ligands of selectins. The specific interactions between SO3Le(a) and E-/P-selectins are critical in the inflammation process. This paper described an efficient synthesis of a lipid conjugate of SO3Le(a) and its combination with phospholipid and cholesterol to form SO3Le(a)-coated liposomes by the freeze-thaw and extrusion method. The size (D = 78 nm) and stability of the resultant glycoliposomes were comparable to that of liposomes without the glycoconjugate. It was further observed that the incorporation of SO3Le(a) into liposomes could significantly enhance their adhesion to activated platelets as a result of the specific binding between SO3Le(a) on the glycoliposome and the P-selectin on activated platelets. The glycoliposome constructs may be useful for antiinflammation or for targeted delivery of drugs to endothelial cells that express E- and P-selectins.
Yan
Feng
F
Department of Chemistry, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA.
Xue
Jie
J
Zhu
Junmin
J
Marchant
Roger E
RE
Guo
Zhongwu
Z
D001665:Binding Sites / Q000187:drug effects; D001792:Blood Platelets / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D019040:E-Selectin / Q000737:chemistry / Q000378:metabolism; D042783:Endothelial Cells; D007983:Lewis Blood Group Antigens / Q000737:chemistry; D008024:Ligands; D050356:Lipid Metabolism; D008055:Lipids / Q000138:chemical synthesis*; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism; D019007:P-Selectin / Q000737:chemistry / Q000378:metabolism; D010316:Particle Size; D015539:Platelet Activation; D010973:Platelet Adhesiveness; D010980:Platelet Membrane Glycoproteins / Q000138:chemical synthesis* / Q000378:metabolism
D019040:E-Selectin; D007983:Lewis Blood Group Antigens; D008024:Ligands; D008055:Lipids; D008081:Liposomes; D009844:Oligosaccharides; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins