Zhang Jingwei, Phetsanthad Ashley, Li Lingjun
Department of Chemistry, University of Wisconsin─Madison, Madison, Wisconsin, USA.
School of Pharmacy, University of Wisconsin─Madison, Madison, Wisconsin, USA.
J Mass Spectrom. 2024 Oct;59(10):e5090. doi: 10.1002/jms.5090.
The study of metal ion's role in the biological processes of Alzheimer's disease has spurred investigations into the coordination chemistry of amyloid beta peptide and its fragments. Nano-electrospray ionization mass spectrometry (nESI-MS) has been utilized to examine the stabilization of bound anions on multiprotein complexes without bulk solvent. However, the effects of anions on metal ion binding interactions with amyloid beta peptide have not been explored. This study directly examined metal-peptide complexes using nESI-MS and investigated the effects of various anions on the binding ratio and stability of these complexes from ammonium salt solutions. The results indicate that different anions have distinct effects on the binding ratio and stability of various metal-peptide complexes. Of these, the bicarbonate ion exhibits the highest binding ratios for metal-peptide complexes, while binding ratios for these complexes in phosphate are comparatively low. Our results suggest that acetate, formate, bicarbonate, and phosphate have weak affinities and act as weak stabilizers of the metal-peptide complex structure in the gas phase. Intriguingly, chloride and sulfate act as stabilizers of the metal-peptide complex in the gas phase. The rank order determined from these data is substantially different from the Hofmeister salt series in solution. Although this outcome was anticipated due to the reduced influence of anions and water solvation, our findings correlate well with expected anion binding in solution and emphasize the importance of both hydration layer and anion-metal-peptide binding effects for Hofmeister-type stabilization in solution. This approach proved useful in examining the interactions between metal ions and amyloid beta peptide, which are relevant to Alzheimer's disease, using direct ESI-MS.
对金属离子在阿尔茨海默病生物学过程中作用的研究，激发了对淀粉样β肽及其片段配位化学的研究。纳米电喷雾电离质谱（nESI-MS）已被用于在无大量溶剂的情况下检测多蛋白复合物上结合阴离子的稳定性。然而，阴离子对金属离子与淀粉样β肽结合相互作用的影响尚未得到探索。本研究使用nESI-MS直接检测金属-肽复合物，并研究了各种阴离子对这些复合物从铵盐溶液中的结合率和稳定性的影响。结果表明，不同阴离子对各种金属-肽复合物的结合率和稳定性有不同影响。其中，碳酸氢根离子对金属-肽复合物的结合率最高，而这些复合物在磷酸盐中的结合率相对较低。我们的结果表明，乙酸根、甲酸根、碳酸氢根和磷酸根亲和力较弱，在气相中作为金属-肽复合物结构的弱稳定剂。有趣的是，氯离子和硫酸根在气相中作为金属-肽复合物的稳定剂。根据这些数据确定的排序与溶液中的霍夫迈斯特盐系列有很大不同。尽管由于阴离子和水合作用的影响减弱，这一结果在意料之中，但我们的发现与溶液中预期的阴离子结合密切相关，并强调了水合层和阴离子-金属-肽结合效应对于溶液中霍夫迈斯特型稳定作用的重要性。这种方法被证明在使用直接电喷雾电离质谱检测与阿尔茨海默病相关的金属离子和淀粉样β肽之间的相互作用方面是有用的。
