化学
肽
硫黄素
电喷雾电离
淀粉样蛋白(真菌学)
体外
糖复合物
生物物理学
蛋白质聚集
立体化学
质谱法
组合化学
生物化学
作者
Sara La Manna,Marilisa Leone,Ilaria Iacobucci,Alfonso Annuziata,Concetta Di Natale,Elena Lagreca,Anna Maria Malfitano,Francesco Ruffo,Antonello Merlino,Maria Chiara Monti,Daniela Marasco
出处
期刊:Inorganic Chemistry
[American Chemical Society]
日期:2022-02-16
卷期号:61 (8): 3540-3552
被引量:6
标识
DOI:10.1021/acs.inorgchem.1c03540
摘要
Neurodegenerative diseases are often caused by uncontrolled amyloid aggregation. Hence, many drug discovery processes are oriented to evaluate new compounds that are able to modulate self-recognition mechanisms. Herein, two related glycoconjugate pentacoordinate Pt(II) complexes were analyzed in their capacity to affect the self-aggregation processes of two amyloidogenic fragments, Aβ21-40 and Aβ25-35, of the C-terminal region of the β-amyloid (Aβ) peptide, the major component of Alzheimer's disease (AD) neuronal plaques. The most water-soluble complex, 1Ptdep, is able to bind both fragments and to deeply influence the morphology of peptide aggregates. Thioflavin T (ThT) binding assays, electrospray ionization mass spectrometry (ESI-MS), and ultraviolet-visible (UV-vis) absorption spectroscopy indicated that 1Ptdep shows different kinetics and mechanisms of inhibition toward the two sequences and demonstrated that the peptide aggregation inhibition is associated with a direct coordinative bond of the compound metal center to the peptides. These data support the in vitro ability of pentacoordinate Pt(II) complexes to inhibit the formation of amyloid aggregates and pave the way for the application of this class of compounds as potential neurotherapeutics.
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