Modulating the Phe–Phe dipeptide aggregation landscape via covalent attachment of an azobenzene photoswitch

Abstract

Synthetic control of peptide-based supramolecular assemblies can provide molecular cues to understand protein aggregation while also inspiring the development of novel chemical biology tools to deliver cargoes inside cells. Here we show that the trans-to-cis photoisomerization of a pendant azo-group covalently attached to a Phe-Phe dipeptide can comprehensively 'turn-off' its native fibrillation propensity as well as provide an optical handle to reversibly switch the aggregate morphology from fibril to vesicle.

Photomodulated Morphologies in Halogen Bond–Driven Assembly during Gel–Sol Transition

“…However, most studies are still focused on the macroscopic state change. On the other hand, a few studies about photomodulated morphology change in supramolecular assemblies rather than gels have been achieved in recent years . For example, a polyoxometalate‐based system containing dimethyldioctadecylammonium and azobenzene moieties underwent a smart morphology change between fibrous and spherical aggregates through tuning the supramolecular interactions by light irradiation .…”

“…For example, a polyoxometalate‐based system containing dimethyldioctadecylammonium and azobenzene moieties underwent a smart morphology change between fibrous and spherical aggregates through tuning the supramolecular interactions by light irradiation . Besides, the photoisomerization of azobenzene group in a phenylalanine–phenylalanine dipeptide could reversibly switch the aggregates from fibril to vesicle . Unfortunately, the well‐defined morphology change of supramolecular assembly during gel–sol transition upon light irradiation still remains a challenge …”

“…On the other hand, a few studies about photomodulated morphology change in supramolecular assemblies rather than gels have been achieved in recent years. [7][8][9][10][11][12][13][14] For ethanol and pyridine group. Thus, we focused on the gel formed in acetonitrile for simplicity.…”

“…[8] Besides, the photoisomerization of azobenzene group in a phenylalanine-phenylalanine dipeptide could reversibly switch the aggregates from fibril to vesicle. [13] Unfortunately, the well-defined morphology change of supramolecular assembly during gel-sol transition upon light irradiation still remains a challenge. [15,16] In general, the non-covalent driving forces for gelation include hydrogen bond, π-π stacking, and van der Waals force.…”

Photo‐Induced Programmable Morphological Transition of the Hybrid Coassembles

“…Azobenzene (AZO), a popular scaffold for preparation of photoresponsive self/coassembly systems due to its efficient and reversible photoisomerization from a thermodynamically stable trans ‐ form to a metastable cis ‐ form, has been widely used as optical switch to manipulate morphology change of assemblies . By introduction of AZO moieties into assemblies, light‐triggered morphology transition from nanoribbon networks to short fibers, fibers to vesicles, and microsphere to vesicles have been achieved. Supramolecular aggregated exhibited an association/dissociation process for differences in molecular volume and dipole moment of AZO moieties under an alternate UV/vis irradiation .…”