Linked Life Data

7996551

Source:http://linkedlifedata.com/resource/pubmed/id/7996551

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
25
pubmed:dateCreated
1995-1-13
pubmed:abstractText
Conformational features of nicardipine in acetonitrile, in the absence and presence of Ca2+, were investigated by one-dimensional NMR and difference absorption spectroscopy techniques. The data show that in acetonitrile solution the antiperiplanar form of nicardipine is dominant. The addition of Ca2+ to the drug solution caused marked changes in the difference absorbance spectra in the 200-400 nm region and in many of its 1H and 13C NMR resonances. The changes were most significant up to a ratio of 0.5 Ca2+:drug. Analysis of the binding data showed the predominant species to be a 2:1 drug:Ca2+ "sandwich" complex with an estimated dissociation constant of 100 microM at 25 degrees C. One-dimensional nuclear Overhauser effect (NOE) experiments revealed through-space connectivities in the drug before and after Ca2+ binding. These changes in conjunction with the changes in 1H and 13C chemical shifts suggest a structure in which the 4-aryl ring substitute of the pyridine moiety moves closer to the C3-side chain in the presence of Ca2+. This attraction is achieved via the chelation of the Ca2+ ion by the oxygen atoms in the m-NO2 of the aryl group and the COOCH2 group in the side chain of the dihydropyridine ring, and gives rise to a stable synperiplanar conformation. A preference for this conformation was also observed in the Ca2+ complex of nifedipine in acetonitrile as inferred from the rather limited NOE data obtained. Our study provides a detailed solution structure for nicardipine and also leads to a suggestion of a role for Ca2+ in the action of this and possibly other dihydropyridines.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4392-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Interaction of calcium channel antagonists with calcium: structural studies on nicardipine and its Ca2+ complex.
pubmed:affiliation
Department of Biochemistry, McMaster University, Hamilton, Ontario, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't