Galaxolide(1,3,4,6,7,8-六氢-4,6,6,7,8-六甲基环戊-γ-2-苯并吡喃;HHCB),Tonalide(7-乙酰基-1,1,3,4,4,6-六甲基-1,2,3,4-四氢萘;AHTN)是“假持久性”污染物,可引起DNA损伤,内分泌干扰,器官毒性,和人类的生殖毒性。HHCB和AHTN很容易在母乳中富集,因此,婴儿接触HHCB和AHTN令人担忧。这里,使用计算模拟和光谱方法研究了HHCB和AHTN与人乳铁蛋白(HLF)相互作用的分子机制,以间接确定HHCB和AHTN如何伤害婴儿。分子对接和动力学模拟研究表明,HHCB和AHTN可以与二级HLF结构相互作用并改变其结构。HHCB对HLF的荧光猝灭,随着HLF-HHCB的形成,AHTN是静态的,HLF-AHTN复合体,并伴随着非辐射能量转移,并且通过相互作用力形成1:1的复合物。时间分辨荧光光谱表明,与小分子的结合不会显着改变HLF荧光寿命。三维荧光光谱表明HHCB和AHTN改变了HLF的肽链主链结构。紫外-可见吸收光谱,同时荧光光谱法,傅里叶变换红外光谱,圆二色谱表明HHCB和AHTN改变了HLF的次级构象。抗菌活性实验表明,多环麝香降低乳铁蛋白活性并与HLF相互作用。这些结果提高了我们对在分子水平上与HLF结合的多环麝香毒性相关机制的理解,并为母婴健康风险评估提供了理论支持。本文受版权保护。保留所有权利。
Galaxolide (1,3,4,6,7,8-hexahydro-4,6,6,7,8-hexamethylcyclopenta-γ-2-benzopyrane; HHCB) and Tonalide (7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene; AHTN) are \"pseudo-persistent\" pollutants that can cause DNA damage, endocrine disruption, organ toxicity, and reproductive toxicity in humans. HHCB and AHTN are readily enriched in breast milk, so exposure of infants to HHCB and AHTN is of concern. Here, the molecular mechanisms through which HHCB and AHTN interact with human lactoferrin (HLF) are investigated using computational simulations and spectroscopic methods to identify indirectly how HHCB and AHTN may harm infants. Molecular docking and kinetic simulation studies indicated that HHCB and AHTN can interact with and alter the secondary HLF structure. The fluorescence quenching of HLF by HHCB, AHTN was static with the forming of HLF-HHCB, HLF-AHTN complex, and accompanied by non-radiative energy transfer and that 1:1 complexes form through interaction forces. Time-resolved fluorescence spectroscopy indicated that binding to small molecules does not markedly change the HLF fluorescence lifetime. Three-dimensional fluorescence spectroscopy indicated that HHCB and AHTN alter the peptide chain backbone structure of HLF. Ultraviolet-visible absorption spectroscopy, simultaneous fluorescence spectroscopy, Fourier-transform infrared spectroscopy, and circular dichroism spectroscopy indicated that HHCB and AHTN change the secondary HLF conformation. Antimicrobial activity experiments indicated that polycyclic musks decrease lactoferrin activity and interact with HLF. These results improve our understanding of the mechanisms involved in the toxicities of polycyclic musks bound to HLF at the molecular level and provide theoretical support for mother-and-child health risk assessments.