Linked Life Data

6195516

Source:http://linkedlifedata.com/resource/pubmed/id/6195516

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1983-12-17
pubmed:abstractText
Structure-activity relationships for binding at site II on human serum albumin have been investigated using drugs, fatty acids, and aliphatic amines with chain lengths C-3 to C-18. A negative charge is not required for binding provided a strongly electronegative center is present. For example, diazepam, a basic drug that exists mainly in the un-ionized form at neutral pH, also binds with high affinity to site II. However, aliphatic amines (pKa values 10-11) with chain lengths C-3 to C-12 did not displace markers from either site I or II, showing that the presence of a positive charge precludes binding at these sites. Short-chain fatty acids, C-3 to C-5, did not displace marker drugs or fluorescent probes from either site I or II when added at equimolar ratios with albumin. Displacement of site II (but not site I) markers occurred with medium-chain fatty acids, C-7 to C-11, and was maximal at C-10. Fatty acids with chain lengths C-10 to C-18 caused an enhancement of fluorescence of dansylamide bound to site I, the maximal effect occurring with C-12. Both arylpropionic acid nonsteroidal anti-inflammatory drugs and medium-chain fatty acids binding at site II had molecular lengths within the range 11-16 A. The effect of hydrophobicity (and/or molecular length) on binding affinity was much more marked with the arylpropionic acids than with the fatty acids, suggesting that bulkier aromatic molecules form more effective interactions at the binding site. The results suggest that site II is a hydrophobic cleft about 16 A deep and about 8 A wide in the albumin molecule with a cationic group located near the surface.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
458-63
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1983
pubmed:articleTitle
Structural requirements for drug binding to site II on human serum albumin.
pubmed:publicationType
Journal Article, In Vitro