Print Email Facebook Twitter Design and synthesis of novel N-acetylgalactosamine-terminated glycolipids for targeting of lipoproteins to the hepatic asialoglycoprotein receptor Title Design and synthesis of novel N-acetylgalactosamine-terminated glycolipids for targeting of lipoproteins to the hepatic asialoglycoprotein receptor Author TNO Preventie en Gezondheid Rensen, P.C.N. van Leeuwen, S.H. Sliedregt, L.A.J.M. van Berkel, T.J.C. Biessen, E.A.L. Publication year 2004 Abstract A novel glycolipid has been prepared that contains a cluster glycoside with an unusually high affinity for the asialoglycoprotein receptor (ASGPr) and a bile acid moiety that mediates stable incorporation into lipidic particles. The glycolipid spontaneously associated with low-density lipoproteins (LDL) and high-density lipoproteins (HDL) within human and murine plasma, and loading of lipoproteins with this glycolipid resulted in an efficient dose-dependent recognition and uptake of LDL and HDL by the liver (and not by spleen) upon intravenous injection into wild-type mice. Preinjection with asialoorosomucoid largely inhibited the uptake, establishing that both HDL and LDL were selectively recognized and processed by the ASGPr on liver parenchymal cells. Finally, repeated intravenous administration of the glycolipid to hyperlipidemic LDL receptor-deficient mice evoked an efficient and persistent cholesterol-lowering effect. These results indicate that the glycolipid may be a promising alternative for the treatment of hyperlipidemic patients who do not respond sufficiently to current cholesterol-lowering therapies. Chemicals / CAS: Acetylgalactosamine, 31022-50-1; Anticholesteremic Agents; Asialoglycoprotein Receptor; Blood Proteins; Glycolipids; Iodine Radioisotopes; Lipoproteins, HDL; Lipoproteins, LDL; Receptors, LDL. Subject Biomedical Researchasialoglycoprotein receptorasialoorosomucoidbile acidglycolipidhigh density lipoproteinhypocholesterolemic agentlow density lipoproteinn acetylgalactosamineanimal cellarticlebinding affinitychemical structuredose responsedrug designdrug synthesishumanhuman cellhyperlipidemialiver cellliver parenchymamalemousenonhumanprotein targetingprotein transportreceptor bindingwild typeAcetylgalactosamineAnimalsAnticholesteremic AgentsAsialoglycoprotein ReceptorBlood ProteinsDrug DesignGlycolipidsHumansHyperlipidemiasIodine RadioisotopesIsotope LabelingLipoproteins, HDLLipoproteins, LDLLiverMiceMice, Inbred C57BLMice, KnockoutProtein BindingReceptors, LDL To reference this document use: http://resolver.tudelft.nl/uuid:2869ccd1-0fea-4d70-8c0b-9303f44f465c DOI https://doi.org/10.1021/jm049481d TNO identifier 238089 ISSN 0022-2623 Source Journal of Medicinal Chemistry, 47 (47), 5798-5808 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.