Temperature dependence of the affinity enhancement of selective adenosine A1 receptor agonism: a thermodynamic analysis
| Autor: | Adriaan P. IJzerman, Palmarisa Franchetti, Alessandro Dalpiaz, Barbara Pavan, Françoise Ngo Ngos |
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| Rok vydání: | 2002 |
| Předmět: |
Agonist
medicine.drug_class Stereochemistry Allosteric regulation CHO Cells Dissociation (chemistry) Adenosine A1 receptor chemistry.chemical_compound Cricetinae Purinergic P1 Receptor Agonists medicine Animals Humans Binding site Pharmacology Binding Sites Trifluoromethyl Dose-Response Relationship Drug Chemistry Receptors Purinergic P1 Temperature Adenosine In vitro Thermodynamics Protein Binding medicine.drug |
| Zdroj: | European Journal of Pharmacology. 448:123-131 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/s0014-2999(02)01982-9 |
| Popis: | The 2-amino-benzoylthiophene derivatives LUF 5468 [(2-amino-4-ethyl-5-methyl-3-thienyl)[3-(trifluoromethyl)phenyl]methanone] and LUF 5484 [(2-amino-4,5,6,7-tetrahydrobenzo[b]thiophen-3-yl)(3,4-dichlorophenyl)methanone] have been shown to allosterically enhance the adenosine A(1) receptor agonist binding. We report a thermodynamic analysis of the agonist affinity obtained at human adenosine A(1) receptors, in the presence and absence of LUF 5468 and LUF 5484. Moreover, an analysis of the temperature dependence for association and dissociation rates of N(6)-cyclohexyladenosine (CHA) binding was performed in the absence and presence of LUF 5484. Thermodynamic data were obtained by affinity measurements performed at different temperatures followed by van't Hoff analysis. The results indicate that the agonist binding is always totally entropy-driven, and that the modulators contribute to decrease the deltaG(o), deltaH(o) and deltaS(o) values. It is concluded that the enhancers are able to increase the non-bonded interactions of the binding site with agonists as CHA, N(6)-cyclopentlyladenosine (CPA), 2'-methyl-N(6)-cyclopentyladenosine (MeCPA) and 2-chloro-2'methyl-N(6)-cyclopentyladenosine (MeCCPA). |
| Databáze: | OpenAIRE |
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