Converting peptides into drugs targeting intracellular protein–protein interactions

Peptides are gaining increasing attention as therapeutics to target intracellular protein–protein interactions that are involved in disease progression. In this review, we discuss how peptides that are able to bind and inhibit a therapeutic target can be translated into drug leads. We discuss the advantages of using peptides as therapeutics to target intracellular protein–protein interactions, chemical strategies to generate macrocyclic peptides that are resistant to proteolytic enzymes, high-throughput screening approaches to identify peptides that have high affinity for therapeutic targets, strategies that permit these peptides to cross cell membranes and so reach intracellular targets, and the importance of investigating their mode-of-action in guiding the development of novel therapeutics.