Optimization of a synthetic arginine receptor. Systematic tuning of noncovalent interactions

被引:69
作者
Rensing, S
Arendt, M
Springer, A
Grawe, T
Schrader, T
机构
[1] Univ Marburg, Fachbereich Chem, D-35032 Marburg, Germany
[2] Univ Dusseldorf, Inst Organ Chem & Makromol Chem, D-40225 Dusseldorf, Germany
关键词
D O I
10.1021/jo0156161
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
The simple arginine binder I could be optimized by strengthening pi -cation as well as electrostatic interactions. Electron-donating or -withdrawing substituents in the 5-position provide experimental evidence for T-cation interactions, because binding energies increase by up to 0.6 kcal/mol due to a single benzene - guanidinium interaction. Even more effective is the introduction of a third phosphonate functionality at the correct distance, so that the guanidinium cation is recognized by optimal electrostatic and hydrogen bond interactions. Monte Carlo simulations and NOESY experiments confirm the expected complex geometries. The optimized host molecule 8 binds arginine half an order of magnitude more efficiently than the parent molecule.
引用
收藏
页码:5814 / 5821
页数:8
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