Azobenzene-Tagged Photopeptides Exhibiting Excellent\nSelectivity and Light-Induced Cytotoxicity in MCF‑7 Cells over\nHeLa and A549

The precise regulation of proteasome activity has become a focal\npoint in current research, particularly its implications in cancer\ntreatment. Bortezomib is used for treating multiple myeloma and is\nfound to be ineffective against solid tumors. A spatiotemporal control\nover the proteasome is one of the solutions to resolve these issues\nusing external stimuli, such as light. Thus, we designed and synthesized\nazobenzene-containing tripeptide vinyl sulfones <b>1</b>, <b>2</b>, <b>3</b>, and <b>4</b>, as the azobenzene moiety\ncan impart E↔Z isomerism upon exposure to UV light. Further,\nthe hydrophobicity of these peptides was fine-tuned by systematically\nvarying the size of hydrophobic amino acids at the P1, P2, and P3\npositions. The light-induced Z isomers of these photopeptides showed\nexcellent cellular potency in HeLa, MCF-7, and A549 cell lines. Photopeptide <b>4</b> with valine at the proximal position, phenylalanine at P2,\nand leucine at the P1 positions exhibited 19.3- and 6.6-fold cellular\npotency in MCF-7 and A549 cells, respectively.