ABSTRACT Because drug discovery efforts have experienced a pronounced decline in productivity, novel approaches to the rational design of new drugs are being introduced and developed. An exciting solution is the use of natural or synthetic peptides and peptidomimetics targeting protein-protein interactions essential for signaling networks function. The combination of several bioinformatic approaches (docking, virtual screening, pharmacophore models, etc.) allows for the use of the vast amount of information on protein-protein interactions deposited in structural databases. In this respect, interacting peptides are susceptible to optimization in order to stabilize or disrupt protein-protein interactions, providing a promising use of peptides and derivatives as therapeutics. In this review we illustrate tools and strategies currently used in peptidomic drug discovery as well as trends in the area of molecular pharmacology.
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