Protein-Protein Interactions: Recent Progress in the Development of Selective PDZ Inhibitors

Title: Protein-Protein Interactions: Recent Progress in the Development of Selective PDZ Inhibitors

Volume: 3 Issue: 2

Author(s): Sylvie Ducki and Elizabeth Bennett

Affiliation:

Keywords: PDZ domain, protein-protein interaction (PPI), PDZ inhibitor

Abstract: Protein-protein interactions (PPI) play an important role in cellular signalling, the most common of which is the PDZ domain. This 90-residue domain occurs 257 times in 142 human proteins. Although these domains have well-defined binding sites which recognises short C-terminal peptide ligands (PLs), the high specificity of PDZ binding makes them an intriguing system to study. Abnormal PPI are of particular importance as they often contribute to the development of diseases. PDZ domains have been reported to be implicated in diseases such as cancer, cystic fibrosis, schizophrenia, Alzheimers, Parkinson, avian influenza, pain, and stroke. In this review, we present the structure of PDZ domains, highlighting the high specificity of their binding to endogenous PLs, leading to their classification. We also consider their involvement in disease pathways and expand on current efforts to modulate their interaction using modified peptides and small molecules as selective PDZ inhibitors.

Cite this article as:

Ducki Sylvie and Bennett Elizabeth, Protein-Protein Interactions: Recent Progress in the Development of Selective PDZ Inhibitors, Current Chemical Biology 2009; 3 (2) . https://dx.doi.org/10.2174/2212796810903020146