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首页> 外文期刊>ACS Omega >Investigation of the Structure and Dynamics of Antiviral Drug Adefovir Dipivoxil by Site-Specific Spin–Lattice Relaxation Time Measurements and Chemical Shift Anisotropy Tensor Measurements
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Investigation of the Structure and Dynamics of Antiviral Drug Adefovir Dipivoxil by Site-Specific Spin–Lattice Relaxation Time Measurements and Chemical Shift Anisotropy Tensor Measurements

机译：抗病毒药物Adefovir DipivoOxil的结构和动力学通过位点特异性旋转晶格弛豫时间测量和化学变换各向异性张量测量

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Adefovir is regarded as a potential antiviral agent. However, it cannot be considered as a valuable drug candidate due to its high polarity that limits its permeability across the human intestinal mucosa. When the ribose phosphate group of adefovir is replaced by the isopolar phosphonomethyl ether functionality, it neutralizes the negative charge of the drug. This makes the drug lipid-soluble and potent to diffuse across the cell membrane. The prodrug adefovir dipivoxil is regarded as a potent antiviral drug against hepatitis B virus (HBV), human immunodeficiency virus (HIV), Rauscher murine leukemia virus (R-MuLV), murine cytomegalovirus (MCMV), herpes simplex virus (HSV), simian immunodeficiency virus (SIV), and feline immunodeficiency virus (FIV). The correlation between the structure and the dynamics of adefovir dipivoxil is determined by measuring the principal components of chemical shift anisotropy (CSA) tensor, site-specific spin–lattice relaxation time, and molecular correlation time at crystallographically different carbon nuclei sites. The CSA parameters, spin–lattice relaxation time, and molecular correlation time of phosphorous nucleus of the organophosphate group of adefovir dipivoxil molecule are also determined. The spin–lattice relaxation time of carbon nuclei varies from 1 to 107 s. The range of molecular correlation time also varies from 10~(–4) to 10~(–8) s. These remarkable diversities of motional dynamics of the molecules imply that there exist various motional degrees of freedom within this valuable drug and these motional degrees of freedom are independent of each other, which may be the reason for the biological activities exhibited by the drug. The correlation between structure and dynamics of such an important antiviral drug adefovir dipivoxil can be visualized by these types of extensive spectroscopic measurements, which will enlighten the path of inventing advanced medicine in the pharmaceutical industry, and it will also illuminate the understanding of the structure–activity relationships of antiviral drug.
机译：Adefovir被认为是潜在的抗病毒药剂。然而，由于其高极性，它不能被认为是有价值的药物候选者，这限制了在人肠粘膜上的渗透性。当AdeFovir的核糖磷酸核磷酸基团被异聚膦酰甲基醚官能团取代时，它中和药物的负电荷。这使得药物脂溶性和有效地扩散在细胞膜上。 Prodrug Adefovir DipivoOxil被认为是抗乙型肝炎病毒（HBV），人免疫缺陷病毒（HIV），Rauscher鼠白血病病毒（R-Mulv），鼠塞细胞病毒（MCMV），单纯疱疹病毒（HSV），Simian免疫缺陷病毒（SIV）和猫直接免疫缺陷病毒（FIV）。通过测量化学移位各向异性（CSA）张量，位点特异性旋转晶格弛豫时间和分子相关时间在晶体不同的碳核位点的分子相关时间来确定结构和动力学之间的相关性和Defovir Dipivoxil之间的相关性。还测定了Adefovir Dipivoxil分子的有机磷酸磷酸核磷核的CSA参数，旋转晶格弛豫时间和分子相关时间。碳核的旋转晶格松弛时间从1到107秒变化。分子相关时间范围也从10〜（4）到10〜（-8）变化。这些众所周知的分子的运动动态多样性暗示了这种有价值的药物中存在各种动态自由度，并且这些动态自由度彼此独立，这可能是药物表现出的生物活性的原因。这种重要的抗病毒药物Adefovir Dipivoxil的结构和动力学之间的相关性可以通过这些类型的广泛的光谱测量来观察，这将引导制药行业的先进药物的路径，并且还将照亮对结构的理解 - 抗病毒药物的活动关系。

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