Modulating inhibitors of transthyretin fibrillogenesis via sulfation: polychlorinated biphenyl sulfates as models.

ABSTRACT: Small molecules that bind with high affinity to thyroxine (T4) binding sites on transthyretin (TTR) kinetically stabilize the protein's tetrameric structure, thereby efficiently decreasing the rate of tetramer dissociation in TTR related amyloidoses. Current research efforts aim to optimize the amyloid inhibiting properties of known inhibitors, such as derivatives of biphenyls, dibenzofurans and benzooxazoles, by chemical modification. In order to test the hypothesis that sulfate group substituents can improve the efficiencies of such inhibitors, we evaluated the potential of six polychlorinated biphenyl sulfates to inhibit TTR amyloid fibril formation in vitro. In addition, we determined their binding orientations and molecular interactions within the T4 binding site by molecular docking

SUBMITTER: Grimm FA 

PROVIDER: S-EPMC4327905 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature