Linked Life Data

7608894

Source:http://linkedlifedata.com/resource/pubmed/id/7608894

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
1995-8-17
pubmed:abstractText
Two series of para-substituted benzenesulfonamides have been examined as inhibitors for bovine carbonic anhydrase II (CAII, EC 4.2.1.1). Both series have hydrophobic alkyl group R connected by amide linkages to the aromatic ring (H2NO2SC6H4-CH2NHCOR1 and H2NO2SC6H4-CONR2R3). The free energy of partitioning (delta Gp) of these ligands between water and octanol had similar, linear correlations with the molecular surface areas of the hydrophobic groups R; delta Gp was only relatively weakly influenced by the linkage to the benzenesulfonamide and the detailed structure of the group R. Binding of these ligands to CAII was more complicated. For compounds having the structure H2NO2SC6H4-L-R, the dependence of the free energy of binding to CAII on the surface area of the hydrocarbon (fluorocarbon) group R for different -L-R was (d delta Gb/dA, kcal/(mol.100 Angstrum 2): -CH2NHCORH, -0.71 +/- 0.03; -CH2NHCORF, -0.72 +/- 0.07; -CONHCH2RH, -2.5 +/- 0.1; and -CONHCH2RF, -2.7 +/- 0.3. The available data permit several conclusions: (i) details (linear, branched, cyclic) of the structure of the group RH are relatively unimportant in determining binding constants (although cyclic structures may bind slightly more strongly than acyclic ligands with the same carbon number); (ii) for a given class of compounds, binding constants of hydrocarbons and fluorocarbons having the same surface area are very similar; and (iii) the nature of the linker L influences the sensitivity of binding to the surface area of the group R, presumably by its influences in positioning the group in the binding pocket of the enzyme. Fluorocarbons seem to be more hydrophobic than hydrocarbons of the same carbon number because they have larger areas of hydrophobic surface; the hydrophobicity of hydrocarbon and fluorocarbon surfaces are similar, after correction for differences in area.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2292-301
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Increasing binding constants of ligands to carbonic anhydrase by using "greasy tails".
pubmed:affiliation
Department of Chemistry, Harvard University, Cambridge, Massachusetts 02138, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.