Work

Probing the Topological Tolerance of Multimeric Protein Interactions: Evaluation of an Estrogen/Synthetic Ligand for FK506 Binding Protein Conjugate

Year: 2010

Type: article

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 high topological tolerance-with such bivalent inhibitors.

Source: Bioconjugate Chemistry

DOI: 10.1021/bc100266v

Authors: Terry W. Moore, Jillian R. Gunther, John A. Katzenellenbogen

Institution: University of Illinois Urbana-Champaign

Language: English

Topic: Estrogen and related hormone effects

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences