An experimental and molecular-modeling study of the binding of linked sulfated tetracyclitols to FGF-1 and FGF-2.
Chembiochem
; 6(10): 1882-90, 2005 Oct.
Article
en En
| MEDLINE
| ID: mdl-16175541
The experimental binding affinities of a series of linked sulfated tetracyclitols [Cyc2N-R-NCyc2, where Cyc = C6H6(OSO3Na)3 and R = (CH2)n (n = 2-10), p-xylyl or (C2H4)2-Ncyc] for the fibroblast growth factors FGF-1 and FGF-2 have been measured by using a surface plasmon resonance assay. The KD values range from 7.0 nM to 1.1 microM for the alkyl-linked ligands. The binding affinity is independent of the flexibility of the linker, as replacement of the alkyl linker with a rigid p-xylyl group did not affect the KD. Calculations suggest that binding modes for the p-xylyl-linked ligand are similar to those calculated for the flexible alkyl-linked tetracyclitols. The possible formation of cross-linked FGF:cyclitol complexes was examined by determining KD values at increasing protein concentrations. No changes in KD were observed; this suggesting that only 1:1 complexes are formed under these assay conditions. Monte Carlo multiple-minima calculations of low-energy conformers of the FGF-bound ligands showed that all of the sulfated tetracyclitol ligands can bind effectively in the heparan sulfate-binding sites of FGF-1 and FGF-2. Binding affinities of these complexes were estimated by the Linear Interaction Energy (LIE) method to within a root-mean-square deviation of 1 kcal mol(-1) of the observed values. The effect of incorporating cations to balance the overall charge of the complexes during the LIE calculations was also explored.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sulfatos
/
Factor 1 de Crecimiento de Fibroblastos
/
Factor 2 de Crecimiento de Fibroblastos
/
Ciclohexanos
Tipo de estudio:
Health_economic_evaluation
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Chembiochem
Asunto de la revista:
BIOQUIMICA
Año:
2005
Tipo del documento:
Article
País de afiliación:
Australia
Pais de publicación:
Alemania