Photo-labile molecules have been widely used not only in organic synthesis but also in biological study. The chemistry of the typical photo-labile organic molecules, including their structure, mechanism underlying their photo-lability and strategies to integrate them with biomolecules, is reviewed to illustrate the structural basis for photo-activable caged compounds. Biological applications of representative photo-labile caged molecules were also illustrated for a general understanding on the important roles of caged compounds in dynamic biological studies. This tutorial review would provide an interdisciplinary overview on the important area of chemical biological study making use of photo-labile caged compounds.

No abstract

We report that phosphotyrosine–cholesterol conjugates effectively and selectively kill cancer cells, including platinum-resistant ovarian cancer cells. The conjugate increases the degree of noncovalent oligomerization upon enzymatic dephosphorylation in aqueous buffer. This enzymatic conversion also results in the assembly of the cholesterol conjugates inside and outside cells and leads to cell death. Preliminary mechanistic studies suggest that the formed assemblies of the conjugates not only interact with actin filaments and microtubules but also affect lipid rafts. As the first report of multifaceted supramolecular assemblies of cholesterol conjugates against cancer cells, this work illustrates the integration of enzyme catalysis and self-assembly of essential biological small molecules on and inside cancer cells as a promising strategy for developing multifunctional therapeutics to treat drug-resistant cancers.

This letter reports the first 2D self-assembly of ABC miktoarm star terpolymers based on dual-responsive polycaprolactonearm-poly(N-isopropylacrylamide)-arm-poly(2-dimethylaminoethyl methacrylate) (μ-CID), which self-assembled into multilayer nanosheets comprising polycaprolactone single crystals in tetrahydrofuran (THF)/ methanol mixed solvents. Interestingly, the nanosheets showed pHresponsive morphological transitions in aqueous solutions, yielding multidimensional assemblies, including 2D hexagonal aggregates, patchy nanofibrils, and patchy vesicles, at different pH values. The nanosheets also exhibited thermoresponsive transition to spherical patchy micelles at a temperature above the lower critical solution temperature (LCST) of the poly(N-isopropylacrylamide) block. This study offers a novel system for fundamental study on the self-assembly of miktoarm star terpolymers.

Because they exhibit important biological functions, from unfolding proteins to activating enzymes to controlling cell fates, aggregates of small molecules are able to serve as functional molecular entities in cellular environments. However, the inability to precisely control their production has hampered the understanding and exploration of their biological functions. Here we show that the well-established ligand-receptor interaction between vancomycin and D-Ala-D-Ala catalyzes the aggregation of a D-Ala-D-Ala-containing small peptide derivative in water. The resulting aggregates largely adhere to the cell surface to induce cell necroptosis. Mutation of D-Ala-D-Ala to L-Ala-L-Ala or removal of the aromatic group in the derivative results in innocuous compounds, confirming that the aromatic-aromatic and ligand-receptor interactions are responsible for the formation and corresponding cytotoxicity of the aggregates. In addition to being the first example of ligand-receptor interaction-catalyzed aggregation of small molecules on the surface of mammalian cells, this work provides useful insights for understanding the cytotoxicity of molecular aggregates of small molecules.