Probing the topological tolerance of multimeric protein interactions: evaluation of an estrogen/synthetic ligand for FK506 binding protein conjugate.

ABSTRACT: Bivalent small molecules composed of a targeting element and an element that recruits endogenous proteins have been shown to block protein-protein interactions in some systems. We have attempted to apply such an approach to disrupt the interaction of the estrogen receptor α with either its associated coactivators or its dimerization partner (i.e., another estrogen receptor). We show here that a conjugate capable of simultaneously binding both the estrogen receptor and a recruited protein (FK506 Binding Protein 12 kDa) is, however, incapable of disrupting the multimeric estrogen receptor dimer/coactivator complex both in vitro and in cell-based reporter gene assays. We postulate why it may not be possible to disrupt this particular protein-protein complex-as well as other systems having hig

SUBMITTER: Moore TW 

PROVIDER: S-EPMC2967433 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature