New class of drugs: stapled peptides

Stapled peptides refers to a computational drug design technique that may create a whole new class of drugs by being able to more effectively target substances within cells and increase the number of proteins which can be targeted. Stapled peptides are generated through the synthetic enhancement of a 3-D alpha-helix protein segment with hydrocarbon bonds to make proteins more rigid and able to penetrate cell walls. The more rigid structure also gives stapled peptides longer lives through greater protease degradation resistance.

The two current classes of drugs, small molecules and biologics, are limited in that they can only target 20% of all proteins. Stapled peptides could allow a wider range of proteins to be used in drug-targeting. They are currently in clinical trials for the inhibition of a BCL-2 family protein, oncogene MCL-1, using an exclusive inhibitor, the MCL-1 BH3 helix, which could unblock caspase-dependent apoptosis in cancer cells (paper).