caPeptide

caPeptide (also known as caPep or R9-caPeptide) is a cell-permeable decoy peptide developed by researchers at the Beckman Research Institute of City of Hope. It corresponds to residues 126–133 of the interdomain connecting loop (IDCL) of proliferating cell nuclear antigen (PCNA), a region that is structurally altered and highly accessible in cancer-associated PCNA (caPCNA). By mimicking this specific domain, caPeptide acts as a competitive inhibitor that disrupts the interaction between PCNA and its essential DNA replication and repair binding partners, such as DNA polymerase delta subunit 3 (POLD3), flap endonuclease 1 (FEN1), and DNA ligase 1 (LIG1). This disruption leads to stalled DNA replication forks, genomic DNA damage, S-phase cell cycle arrest, and apoptosis in cancer cells. To facilitate cellular uptake, the peptide is typically fused to a nine D-arginine cell-penetrating peptide sequence (R9) with a two-cysteine linker, forming R9-caPeptide. It has demonstrated selective cytotoxicity in breast cancer, neuroblastoma, pancreatic cancer, and lymphoma models, while sparing non-malignant cells.

Other names

R9-caPepR-9-caPepR 9-caPepR9-caPeptideR-9-caPeptideR 9-caPeptideR9-cc-caPeptideR-9-cc-caPeptideR 9-cc-caPeptidecaPep