All-hydrocarbon stapled peptides as Synthetic Cell-Accessible Mini-Proteins

A majority of proteins responsible for the establishment and maintenance of human disease states are unable to be targeted therapeutically by molecules belonging to either of the two established classes of drugs, namely small molecules and protein therapeutics. Recent efforts toward drugging these ‘undruggable’ proteins have led to greatly increased focus on cell-penetrating mini-proteins as a new class of agents for targeting intractable intracellular proteins. These molecules are designed to combine the advantages intrinsic to each conventional therapeutic modality while overcoming their individual limitations. One class of cell-penetrating mini-proteins, all-hydrocarbon stapled peptides, has recently demonstrated the ability to potently and specifically target previously intractable proteins such as transcription factors, vaulting this class to the forefront of a new wave of next-generation drugs.