The interactions of phenytoin and its binding site in DI-S6 segment of Na+ channel voltage-gated peptide by NMR spectroscopy and molecular modeling study

B. S. Lou*, T. H. Lin, C. Z. Lo

*此作品的通信作者

研究成果: Article同行評審

4 引文 斯高帕斯(Scopus)

摘要

Nuclear magnetic resonance (NMR) spectra of a model peptide (BL-DIS6), in the presence of anticonvulsant diphenyl drug, phenytoin (DPH), were measured to obtain the interactions between the selected drug and the model peptide. BL-DIS6's sequence corresponds to the S6 segment in domain I of rat brain type IIA Na+-channel. NMR studies have demonstrated that the magnitude of the chemical shifts of amide- and α-protons can be used as a measurement of the complex stability and binding site of the peptide. Our NMR results propose a 310-helical structure for BL-DIS6, and suggest a binding cavity for DPH that involves the hydrophobic particles of residues Ans-7, Leu-8, Val-11, and Val-12. Furthermore, molecular modeling was performed to provide a possible complex conformation that the phenyl portion of DPH is accommodated in the proximity of the C-terminal residues Ala-11 and Val-12, and simultaneously the heterocyclic amine ring of DPH is perching at the residue Asn-7 periphery and stabilizing the phenyl portion deep insertion into the peptide. Copyright Blackwell Munksgaard, 2005.

原文English
頁(從 - 到)27-38
頁數12
期刊Journal of Peptide Research
66
發行號1
DOIs
出版狀態Published - 7月 2005

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