In silico Docking Studies of Fingolimod and S1P1 Agonists.

摘要: The sphingosine-1-phosphate receptor 1 (S1P1), originally the endothelial differentiation gene (EDG-1), is one of five G protein-coupled receptors (GPCRs) S1P1 - 5 that bind to and are activated by (S1P). lipid S1P an intermediate in sphingolipid homeostasis, a major medical target for immune system modulation; agonism produces myriad biological responses, including cell barrier integrity, chemotaxis, lymphocyte trafficking/targeting, angiogenesis, as well regulation cardiovascular system. Use silico docking simulations on crystal structure allows pinpointing residues within receptor's active site actively contribute binding S1P, point how these specific interactions can be exploited design more effective synthetic analogs specifically presence closely related S1P2, S1P3, S1P4, S1P5. We examined properties endogenous substrate selection sphingosine-derived modulators with using software package Molecular Operating Environment® (MOE®). modeling studies reveal relevance phosphorylation, i.e., phosphate or phosphonate moiety successful occur, indicate which responsible most prominent (S1PR) modulators, fingolimod its structural relatives. Furthermore, trends steric preferences enantiomers could observed, facilitating future receptor-specific substrates precisely S1P1.