Accepted_test

Bioinformatic search for low-molecular-weight ligands ligands of the glycated form of human serum albumin capable of modu-lating its interaction with amyloid β peptide
by Litus Ekaterina | Shevelyova Marina | Machulin Andrey | Deryusheva Evgenia | Institute for Biological Instrumentation, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, Pushchino, Russia | Institute for Biological Instrumentation, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, Pushchino, Russia | Skryabin Institute of Biochemistry and Physiology of Microorganisms, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, Pushchino, Russia | Institute for Biological Instrumentation, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, Pushchino, Russia
Abstract ID: 187
Event: BGRS-abstracts
Sections: [Sym 9] Section “Molecular Pathology, Diagnostics, and Therapeutics”

Alzheimer disease (AD) is one of the most prevalent dementia forms that pose a serious society problem. The key mechanism of AD development is amyloid-β peptide (Aβ) accumulation in brain tissue leading to amyloid plague formation. Human serum albumin (HSA) plays important role in the Aβ transport and may influence on the Aβ plague formation. Wherein ligands of HSA may modulate its affinity for the Aβ. For further development, it is necessary to study under conditions that more fully correspond to in vivo conditions. It is known, for example, that the level of glycated HSA in serum of patients with diabetes mellitus associated with AD is increased, but the influence of HSA ligands on the affinity of the glycated HSA for Aβ has not been studied. In this work, we searched for low-molecular weight ligands of the glycated HSA that can modulate its interaction with Aβ. DrugBank drug database was used as a main data source to form a panel of 100 HSA ligands associated with AD. Complexes of the selected ligands with HSA were modeled using AutoDockVina software. 8 drugs (Metoprolol, Fluorouracil, Testosterone, Flurbiprofen, Estradiol, Salicylic acid, Abiraterone, Enalapril) potentially capable of modulating the interaction of the glycated form of HSA with Aβ were selected based on modeling data and literature data on HSA glycation sites (via lysine and arginine residues). The obtained data can be used for repurposing of drugs in the development of personalized approach to the treatment and prevention AD in patients with concomitant diabetes mellitus.