Conditional Activation of Protein Therapeutics by Templated Removal of Peptide Nucleic Acid Masking Groups.

ABSTRACT: Interleukin-2 (IL-2)-based therapeutics are emerging as treatments for immunotherapy; however, systemic activation of immune cells hampers their success. Chemically controlling the activity of potent cytokines could mitigate unwanted T cell stimulation and widen their therapeutic window. In this study, we developed a strategy for the conditional activation of proteins utilizing removable peptide nucleic acid (PNA) masking groups. Site-specific installation of "Lock"-PNAs containing a cleavage thioester linkage enabled steric blockage of receptor binding sites. Rapid unmasking and activation were performed by the addition of a complementary "Key"-PNA containing a cysteine (Cys) residue, which forms a PNA-PNA duplex leading to a proximity-accelerated cleavage step and release of the active p

SUBMITTER: Gless BH 

PROVIDER: S-EPMC12087824 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature