Solid-Phase Synthesis of Sequence-Defined Self-Immolative Oligocarbamates for Molecular Recognition

Sequence-defined macromolecules offer a powerful platform for encoding molecular function with high precision, yet their integration with self-immolative architecture remains underexplored. Herein, we report a solid-phase strategy to synthesize discrete self-immolative oligo(benzyl carbamates) with programmable sequences and chain lengths. Triggered removal of an ortho-nitrobenzyl terminus initiates rapid head-to-tail depolymerization, while selective fragmentation of benzylic carbamate linkages under matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) tandem mass spectrometry enables direct sequence readout. Leveraging these features, a small one-bead one-compound (OBOC) library of resin-bound oligocarbamates was constructed and screened against the water-insoluble photosensitizer temoporfin. Distinct sequences exhibited pronounced, sequence- and length-dependent recognition of temoporfin, which was further supported by computational analysis. This work establishes sequence-defined self-immolative oligocarbamates as a programmable, decodable, and stimulus-responsive platform for ligand discovery and molecular recognition.