Open AccessMelatonin binds with high affinity and specificity to beta‐amyloid: LC‐MS provides insight into Alzheimer’s disease treatment
Author(s) -
Dai Yaqian,
Peng Liduo,
Liu Yajing,
Xu Yuanhong,
Qiao Jinping
Publication year - 2021
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.13279
Subject(s) - melatonin , chemistry , melatonin receptor , dissociation constant , alzheimer's disease , amyloid beta , peptide , medicine , receptor , endocrinology , biochemistry , biology , disease
To study the potential relationship between melatonin and beta‐amyloid (Abeta), we established a liquid chromatography–mass spectrometry (LC‐MS) method to quantitatively analyze melatonin, deuterated isotopes (melatonin‐D4), and internal standard 6‐iodo‐2‐(4'‐dimethylamino‐) phenyl‐imidazo(1,2) pyridine (IMPY) under positive (+) mode. The gradient elution was set to 6 min, and the corresponding peak time of melatonin and its isotope melatonin‐D4 was 3.14 min, while the peak time for the internal standard IMPY was 3.24 min. Next, we established and optimized the molecule receptor saturation binding assay based on LC‐MS to determine the melatonin affinity for beta‐amyloid (Abeta). Melatonin showed a high and specific binding for Abeta. The corresponding equilibrium dissociation constant ( K d) of melatonin with Abeta 1‐40 and Abeta 1‐42 was 814.37 ± 36.62 and 628.33 ± 13.57 nmol·L −1 ; besides, the K d of melatonin with mixed plaques (1‐40 and 1‐42) was 461.13 ± 45.37 nmol·L −1 . The results may suggest the potential mechanism of action of MT on Abeta and provide a theoretical basis for the improvement of MT treatment of Alzheimer's disease.