title: Binding of glyco-acridine derivatives to lysozyme leads to inhibition of amyloid fibrillization.
abstract: While amyloid-related diseases are at the center of intense research efforts, no feasible cure is currently available for these diseases. The experimental and computational techniques were used to study the ability of glyco-acridines to prevent lysozyme amyloid fibrillization in vitro. Fluorescence spectroscopy and atomic force microscopy have shown that glyco-acridines inhibit amyloid aggregation of lysozyme; the inhibition efficiency characterized by the half-maximal inhibition concentration IC50 was affected by the structure and concentration of the derivative. We next investigated relationship between the binding affinity and the inhibitory activity of the compounds. The semiempirical quantum PM6-DH+ method provided a good correlation pointing to the importance of quantum effects on the binding of glyco-acridine derivatives to lysozyme. The contribution of linkers may be explained by the valence bond theory. Our data provide a basis for the development of new small molecule inhibitors effective in therapy of amyloid-related diseases.
authors: Institute for Computational Science and Technology, 6 Quarter, Linh Trung Ward, Thu Duc District, Ho Chi Minh City, Vietnam.
authors: Quan Van
authors: QV
authors: Vuong
authors: Katarina
authors: K
authors: Siposova
authors: Trang Truc
authors: TT
authors: Nguyen
authors: Andrea
authors: A
authors: Antosova
authors: Lucia
authors: L
authors: Balogova
authors: Ladislav
authors: L
authors: Drajna
authors: Jan
authors: J
authors: Imrich
authors: Mai Suan
authors: MS
authors: Li
authors: Zuzana
authors: Z
authors: Gazova
mesh_terms: D000166:Acridines / Q000737:chemistry / Q000378:metabolism*; D000682:Amyloid / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000686:Amyloidosis; D006801:Humans; D009113:Muramidase / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D000166:Acridines; D000682:Amyloid; D016229:Amyloid beta-Peptides; D009113:Muramidase