Peptide Self-Assembly Controlled Photoligation of Polymers

Highly efficient chemical ligations that operate in waterundermild conditions are the foundation of bioorthogonal chemistry. However,the toolbox of suitable reactions is limited. Conventional approachesto expand this toolbox aim at altering the inherent reactivity offunctional groups to design new reactions that meet the required benchmarks.Inspired by controlled reaction environments that enzymes provide,we report a fundamentally different approach that makes inefficientreactions highly efficient within defined local environments. Contrastingenzymatically catalyzed reactions, the reactivity controlling self-assembledenvironment is brought about by the ligation targets themselves avoidingthe use of a catalyst. Targeting [2 + 2] photocycloadditions, whichare inefficient at low concentrations and readily quenched by oxygen,short & beta;-sheet encoded peptide sequences are inserted betweena hydrophobic photoreactive styrylpyrene unit and a hydrophilic polymer.In water, electrostatic repulsion of deprotonated amino acid residuesgoverns the formation of small self-assembled structures, which enablea highly efficient photoligation of the polymer, reaching & SIM;90%ligation within 2 min (0.034 mM). Upon protonation at low pH, theself-assembly changes into 1D fibers, altering photophysical propertiesand shutting down the photocycloaddition reaction. Using the reversiblemorphology change, it is possible to switch the photoligation "ON"or "OFF" under constant irradiation simply by varyingthe pH. Importantly, in dimethylformamide, the photoligation reactiondid not occur even at 10-fold higher concentrations (0.34 mM). Theself-assembly into a specific architecture, encoded into the polymerligation target, enables a highly efficient ligation that overcomesthe concentration limitations and high oxygen sensitivity of [2 +2] photocycloadditions.