Yating Lei , Zihang Zhang , Xiulan Ma , Ruirui Cai , Lulu Dai , Ying Guo , Xun Tuo
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引用次数: 1
Abstract
Perampanel (PER) is the first drug to treat epilepsy by blocking α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. In the current study, the interaction of PER and calf thymus DNA (ctDNA) was explored through various spectroscopic techniques and computer modelling. According to the UV-vis titration results, PER combined with ctDNA via groove binding, which was also confirmed by thermal melting, salt effect, ssDNA/dsDNA quenching, and competitive experiments. The dominant forces were hydrogen bond and van der Waals force. And the binding constant obtained was 6.97 × 103 M−1 at 298 K. According to the data from FTIR assays and computer modelling, PER was embedded in the minor groove of ctDNA rich in A and T bases. In the simulation of 200 ns, the PER-DNA system reached equilibrium at about 100 ns. The structure of DNA became loose when a stable binary complex with PER was formed. The energy decomposition indicated that DC-9, DT-19, and DT-20 bases played a main role in this complex-forming. In summary, this study contributed to understanding the interaction mechanism of PER and ctDNA.
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