biostudies-literatureZafar HNational Science Foundation Graduate Research Fellowship ProgramNational Cancer InstituteNCI NIH HHS571-576https://www.ebi.ac.uk/biostudies/studies/S-EPMC12323701biostudies-literatureUnknown13(5)Controlling the access of proteases to cleavable peptides placed at specific locations within macromolecular architectures represents a powerful strategy for biologically responsive materials design. Here, we report the synthesis of peptide-containing <i>bivalent</i> bottlebrush (co)polymers (BBPs) featuring polyethylene glycol (PEG) and 7-amino-4-methylcoumarin (AMC) pendants on each backbone repeat unit. The AMCs are linked via caspase-3-cleavable peptides which, upon enzymatic cleavage, provide a "turn-on" fluorescence signal due to the release of free AMC. Time-dependent fluorscence measurements demonstrate that the caspase-3-induced peptide cleavage and AMC release from BBPs is strongly dependent on the BBP backbone length and the AMC-peptide linker location within the BBP architecturACS macro lettersCaspase-3-Responsive, Fluorogenic Bivalent Bottlebrush Polymers.PMC12323701R01 CA2204682R01CA220468-06A1Nguyen HVZafar HLiu BJohnson JAfalseCaspase-3-Responsive, Fluorogenic Bivalent Bottlebrush Polymers.Controlling the access of proteases to cleavable peptides placed at specific locations within macromolecular architectures represents a powerful strategy for biologically responsive materials design. Here, we report the synthesis of peptide-containing <i>bivalent</i> bottlebrush (co)polymers (BBPs) featuring polyethylene glycol (PEG) and 7-amino-4-methylcoumarin (AMC) pendants on each backbone repeat unit. The AMCs are linked via caspase-3-cleavable peptides which, upon enzymatic cleavage, provide a "turn-on" fluorescence signal due to the release of free AMC. Time-dependent fluorscence measurements demonstrate that the caspase-3-induced peptide cleavage and AMC release from BBPs is strongly dependent on the BBP backbone length and the AMC-peptide linker location within the BBP architectur2024-01-01T00:00:00Z2024 May2026-03-31T11:48:52.604Z2025-09-01T03:05:36.099ZS-EPMC123237013864717810.1021/acsmacrolett.4c00119