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Updated: Jul 19, 2026

Peptide-based Identification of Functional Motifs and their Binding Partners
Published on: June 30, 2013
Reining in Multidrug Resistance Protein 1 via Binding Its Flexible Interdomain Linker with Sequence-Selective
Avijit Ghosh1, Mansi Sharma1, Yan Zhao1
1Department of Chemistry, Iowa State University, Ames, Iowa 50011-3111, United States.
None:
Overexpressed ATP-binding cassette (ABC) transporters, such as multidrug resistance protein 1 (MRP1) encoded by ABCC1, are responsible for multidrug resistance in anticancer treatment due to their abilities to prevent drugs from reaching their lethal intracellular concentrations. Similar overexpression of drug efflux pumps is a major contributor to antimicrobial resistance seen in bacteria. We report sequence-selective, molecularly imprinted nanoparticles (MINPs) targeting MRP1 in human cancer cells. These nanoparticles mask different segments of the long, flexible linker connecting NBD1 (nucleotide-binding domain 1) and TMD2 (transmembrane domain 2) of MRP1. Binding of the protein near the inner membrane interface is found to strongly inhibit the function of the efflux pump and sensitize Dox-resistant cancer cells to the drug, reducing its IC50 value by ∼25%. These results illustrate a new strategy for inhibiting intracellular proteins and identifying potential functional linear motifs in unstructured regions of proteins, benefiting from the facile preparation of the MINPs for different peptide sequences, their highly specific binding abilities, and their ability to enter cells.
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