Spatiotemporal Resolved Live Cell Membrane Tracking through Photo‐click Reactions Enriched in Lipid Phase

Abstract

A set of photo‐switchable monopeptides derived from cis‐β‐dibenzodiazocine‐l‐alanine (cis‐DBDAA) have been designed and synthesized, which are capable of photo‐click reacting with diaryltetrazoles or diarylsydnones in a hydrophobic phospholipid bilayer environment. The DBDAA monopeptides include both a hydrophobic tail on C‐terminal, providing high affinity toward lipid membrane, and a modularized functional moiety on N‐terminal, enabling rapid optimization of the self‐assembly strength to form multifunctional supramolecules. With the cis‐DBDAA monopeptides photo‐switched into trans‐configuration, we were able to disrupt the supramolecular assembly through an efficient photo‐click reaction across the lipid bilayer of liposomes. We reveal that the performance of the photo‐click reactions between the monopeptides and photo‐generated nitrile imine intermediates is significantly enhanced by enrichment of both reactants in the hydrophobic membrane lamel of liposomes. Enrichment of the DBDAA monopeptide in lipid phase serves as a convenient method to introduce bioorthogonal chemical handles on live cell membranes, which enables fluorescence labelling of single cell's membrane with high spatiotemporal resolution to facilitate the studies on cell membrane dynamics.

A facile and light-controllable drug combination for enhanced photopharmacology

“…11 Recently, a significant advance was also made in utilizing the direct ring-strain in situ loading of cyclic azobenzene under visible-light irradiation for accelerated bioorthogonal ligation and fluorescence labelling with spatiotemporal controllability by our group. 12 Besides, we are also interested in exploring photo-switchable molecules for bioorthogonal chemistry and broader and practical biological applications.…”

Dibenzo[b,f][1,4,5]chalcogenadiazepine Photoswitches: Conversion of Excitation Energy into Ring Strain

“…[36] Comparing with linear azobenzene, they disclosed that the cyclic structure of DBDA led to red-shifted n-π* transition bands in both isomers for excellent photochromic merit, enhanced quantum yields during photo-switching and energized isomers in trans-configuration with high ring-strain energy (Scheme 1a). Then, by introducing heteroatoms on the bridging moiety, e.g., À CH 2 À OÀ , À CH 2 À SÀ and À CH 2 À NRÀ , [30][31][32][33] the excitation wavelength can be further extended to near-infrared region in aqueous medium, which has been scouted for functional control of neurotransmitters (ionotropic kainate receptors), [37] reversible folding and unfolding of secondary and tertiary structure of peptides or proteins [38][39][40] as well as regulation of kinase inhibitor efficacy. [41,42] Intriguingly, the light driven Z!E isomerization of DBDA also allows photo-energy to be transformed into chemical-energy stored in the form of ringstrain, accompanied by a unique configurational reforming from "bowl" to "crown" shape (Scheme 1a).…”

“…[36] The rigidity of entire polycyclic system can then be subtly tuned by fusing extra ring substructures, thereby boosting the energy harvesting capacity during photoisomerization, and this is realized by diindane DBDA with up to 18 % light-tochemical energy conversion efficiency (η). [35] Unexpectedly, DBDA can also serve as a dipolarophile in cycloaddition with nitrilimines, and the in situ harvested ring-strain energy in trans-configuration was capable of accelerating the cycloaddition rate, [38,40] which is akin to the ring-strain promotion via trans-cyclooctene (TCO). [43] Methylene-, [44] oxygen-and sulfur-bridged dibenzodiazepines [45] are the simplest seven-membered cyclic azobenzenes, first synthesized back in 1959-1962.…”