The binding of xanthone derivatives to transthyretin.
A series of xanthone derivatives, isolated from Calophyllum teysmannii var. inophylloide, have been evaluated for their binding affinity to transthyretin. Transthyretin is a plasma protein involved in the transport of thyroxine (T4) and also implicated in amyloid diseases. Using competition-binding studies with the protein natural ligand T4, we have identified one prenylated xanthone with a very strong affinity to transthyretin. Molecular docking simulations show that the flexible tail of the prenylated xanthone could allow favorable molecular interactions. Since this xanthone may play a role in the thyroxine metabolism and/or over the pathogenic process associated with the amyloid disease, these results may be explored for the design of new ligands.
Maia
Filipe
F
Unidade de Estrutura Molecular, IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, 4150-180 Porto, Portugal.
Almeida
Maria do Rosário
Mdo R
Gales
Luís
L
Kijjoa
Anake
A
Pinto
Madalena M M
MM
Saraiva
Maria J
MJ
Damas
Ana M
AM
D001667:Binding, Competitive; D003461:Crystallography; D006801:Humans; D011228:Prealbumin / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D044004:Xanthones / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
D011228:Prealbumin; D044004:Xanthones