Linked Life Data

7783116

Source:http://linkedlifedata.com/resource/pubmed/id/7783116

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1995-7-18
pubmed:abstractText
Cholesterol-derivatized galactosides have been devised in order to induce liver uptake of lipoproteins via the galactose-recognizing asialoglycoprotein receptor in the liver. In this study we describe the derivatization of a newly developed triantennary cluster galactoside having high affinity for the asialoglycoprotein receptor, N-[[tris-O-(3,6,9-trioxaundecanyl-beta-D-galactopyranosyl)metho xym ethyl] -N alpha-[1-(6-methyladipyl)]glycinamide (TG(20A)) with cholesterol. Hereto, TG(20A) was coupled to glycine-(5-cholesten-3 beta-yl ester) in the presence of (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate, affording N-[[tris-O-(3,6,9-trioxaundecanyl-beta-D- galactopyranosyl)methoxymethyl]methyl]-N alpha-[1-(6-(5-cholesten-3 beta-yloxy)glycyl)adipyl]glycinamide (TG(20A)C) in 46% yield. This compound is an amphiphilic, water-soluble compound. In aqueous solution it readily formed small micelles (4.9 +/- 1.2 nm) consisting of approximately 20 molecules. Upon incubation with human serum, TG(20A)C spontaneously incorporated into the most prominent serum lipoproteins, i.e., low-density lipoprotein (LDL) and high-density lipoprotein (HDL), thereby inducing an increase in buoyant density of these lipoproteins. The integrity of HDL and LDL, as judged from particle size analysis of both lipoproteins, was not altered by incubation with up to 0.33% of TG(20A)C (w/v). Following intravenous bolus injection into rats, TG(20A)C induced a dose-dependent decrease in the serum cholesterol content of maximally 44%, at a dose of 1.9 mg kg-1. This makes TG(20A)C at least 30-fold more effective than the previously developed N-[[tris-O-(beta-D-galactopyranosyl)methyl]methyl]-N alpha-[4-(5- cholesten-3 beta-yloxy)succinyl]glycinamide (TG(4A)C), provided with a cluster galactoside that displayed a 2000-fold lower affinity for the asialoglycoprotein receptor than TG(20A). In conclusion, the hypocholesterolemic activity of a cholesterylated galactoside can be strongly enhanced by using a cluster galactoside with higher affinity for the asialoglycoprotein receptor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1846-52
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
The cholesterol derivative of a triantennary galactoside with high affinity for hepatic asialoglycoprotein receptor: a potent cholesterol lowering agent.
pubmed:affiliation
Division of Biopharmaceutics, Leiden-Amsterdam Center for Drug Research, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't