ISSN:
0947-6539
Keywords:
carbohydrates
;
molecular modeling
;
preorganization
;
sialyl Lewisx
;
selectins
;
Chemistry
;
General Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
A molecular modeling tool for the rational design of E-selectin antagonists based on the lead structure sialyl Lewisx has been developed. The binding affinity to the receptor is considerably influenced by the entropy and consequently by the antagonist's ability to place its pharmacophores in an optimal spatial arrangement, i.e., by its preorganization for binding. The computational model assesses the preorganization of a potential selectin antagonist with the aid of Monte Carlo (jumping between wells)/stochastic dynamics [MC(JBW)/SD] simulations. The model has been validated by correlating preorganization and bioactivity of several selectin antagonists. The results suggest that only preorganized compounds are likely to bind to E-selectin.
Additional Material:
7 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/chem.19970031006
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