Tau‐Derived Peptides Bearing Azobenzene on Side Chains for Light‐Controllable Microtubule Polymerization

The precise control of microtubule dynamics is essential for diverse cellular processes and is a promising target for optical regulation using photoresponsive molecules. In this study, we developed Tau-derived peptides bearing azobenzene moieties on their side chains that enabled reversible photocontrol of microtubule polymerization by binding to the inside of microtubules. Two peptide derivatives with azobenzene located at different positions were synthesized by simple on-resin Fmoc solid-phase chemistry. Confocal microscopy and competition assays confirmed that both derivatives target the Taxol-binding pocket inside microtubules. Although both cis- and trans-forms bound microtubules, only the cis-form of one derivative (cis-TMR-Azo-TP2) significantly enhanced microtubule polymerization with longer lengths compared with the corresponding trans-form (trans-TMR-Azo-TP2). Moreover, light-dependent switching of microtubule length was achieved via photoisomerization. These findings highlight azobenzene-functionalized Tau-derived peptides as a versatile platform for achieving spatiotemporal control over microtubule polymerization using optical stimuli.