Protein-protein interactions (PPIs) are central to living systems, as protein recognition represents the molecular event at the basis of many physiological and pathological conditions. Therefore, PPIs have attracted considerable attention for their therapeutic implications. However, the discovery of molecules able to target PPIs is a challenging effort. In fact, while PPIs exhibit large surface contact areas in which numerous low energetic interactions occur, they lack deep binding cavities, making them difficult to target for with small molecules. Because of their physical properties, peptides are, instead, exploited by Nature to interact with proteins, and represent the preferred molecules in the search for novel agents able to target PPIs, to modulate, activate or inhibit, the associate biological response.
The sequencing of genomes, and the analysis of interactomes, biochemical and structural studies, have provided a vast amount of information on protein-protein interactions and networks. However, only a tiny fraction of these possible PPI targets has been challenged by peptide modulators, leaving an unexplored research space for the development of novel drugs, diagnostics and molecular tools for chemical biology applications. In order to strengthen the output in this research area, it is important to have a forum highlighting successful applications of peptides targeting PPIs, and update the methodologies employed to develop them. In this way, this Research topic intends to stimulate the interest in peptides targeting PPIs to achieve sophisticated molecular tools for the most disparate applications in biomedicine and chemical biology.
The aim of this Research Topic is to spotlight successful examples of peptides, which targeting a protein-protein recognition site, are able to modulate a biological response or bind to a specific protein. The interest is to highlight promising and compelling approaches (experimental or computational) used to develop bioactive peptides/peptidomimetics with emphasis on the recent advances in the field. Biophysical and biochemical studies aimed to understand or to improve peptide-protein binding mode/affinity or peptide-protein activation/inhibition mechanism are also welcome.
Authors are invited to submit reviews and original research articles exploring peptide targeting PPIs themes including, but not limited to:
• Peptide design by structure-based and/or computational methodologies.
• Screening of chemical or biological peptide libraries.
• Design of peptides as allosteric modulators as well as stabilizers of PPIs.
• Development of peptidomimetics, cyclic peptides, conformationally constrained peptides, protein mimics.
• Methods for the analysis of peptide-protein interactions.
A full list of accepted article types including descriptions can be found at this
link