Linked Life Data

18420145

Source:http://linkedlifedata.com/resource/pubmed/id/18420145

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-4-18
pubmed:databankReference
pubmed:abstractText
Vitamin D nuclear receptor (VDR), a ligand-dependent transcriptional regulator, is an important target for multiple clinical applications, such as osteoporosis and cancer. Since exacerbated increase of calcium serum level is currently associated with VDR ligands action, superagonists with low calcium serum levels have been developed. Based on the crystal structures of human VDR (hVDR) bound to 1alpha,25-dihydroxyvitamin D(3) and superagonists-notably, KH1060-we designed a superagonist ligand. In order to optimize the aliphatic side chain conformation with a subsequent entropy benefit, we incorporated an oxolane ring and generated two stereo diasteromers, AMCR277A and AMCR277B. Only AMCR277A exhibits superagonist activity in vitro, but is as calcemic in vivo as the natural ligand. The crystal structures of the complexes between the ligand binding domain of hVDR and these ligands provide a rational approach to the design of more potent superagonist ligands for potential clinical application.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1074-5521
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
383-92
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Structure-based design of a superagonist ligand for the vitamin D nuclear receptor.
pubmed:affiliation
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Département de Biologie et de Génomique Structurales, Université Louis Pasteur, Strasbourg F-67000, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't