E6AP-mimicking peptide (compound 13) is a high-affinity, selective, irreversible, and potent peptide-based covalent inhibitor of the HPV16 E6 oncoprotein, utilizing a cysteine-reactive acrylamide warhead to target 16E6. The E6AP-mimicking peptide has an inhibition constant (Ki) of 17 nM and targets all residues emerging in the E6 binding pocket to disrupt the 16E6 and E6AP binding interface. It selectively binds and cross-links MBP-16E6 in PBS or protein mixtures.