The present invention relates to inhibitors of protein-protein interactions (PPI). Specifically, the present invention relates to a structural informatics approach to designing peptidomimetic macrocycles containing an amino acid “warhead” for ligand-directed covalent modification of cysteine and lysine-containing proteins for the treatment of diseases such as cancer. Further included is the targeting of components of the BCL2 signaling pathway, specifically BCL2-A1 and MCL-1.
