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Scheme 1. Photoinduced Supramolecular Dimerization of FGG Peptide Mediated by the Light-Triggered Transformation of a 1:1 into a 2:1 Ligand−ReceptorComplex, Formed between CB8 and NVoc-FGG or FGG a
Source publication
The selective photodeprotection of the NVoc-modified FGG tripeptide yields the transformation of its 1:1 receptor-ligand complex with cucurbit[8]uril into a homoternary FGG2@CB8 assembly. The resulting light-induced dimerization of the model peptide provides a tool for the implementation of stimuli-responsive supramolecular chemistry in biologicall...
Citations
... [26,[37][38][39][40][41] Although the choice of light as a stimulus presents recognized advantages, such as remote application and high spatiotemporal control, light-responsive CBn-based (pseudo)rotaxanes, and host-guest complexes in general, have been less frequently reported. [42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] This is likely due to the fact that the outcome of photoinduced conformational changes, observed in typical photochromic compounds, on the stability of the CBn-based host-guest systems is more difficult to predict. ...
A linear double pyridinium‐terminated thread comprising a central chalcone moiety is shown to provide two independent binding sites with similar affinity for cucurbit[7]uril (CB7) macrocycles in water as judged from NMR, UV‐Visible and fluorescence spectroscopies. Association results in [2] and [3]pseudorotaxanes, which are both pH and photosensitive. Switching from the neutral chalcone to the cationic flavylium form upon irradiation at 365 nm under acidic conditions provided an enhanced CB7 association (K1:1 increases from 1.2×10⁵ M⁻¹ to 1.5×10⁸ M⁻¹), limiting spontaneous on‐thread cucurbituril shuttling. This co‐conformational change in the [2]pseudorotaxane is reversible in the dark with kobs=4.1×10⁻⁴ s⁻¹. Threading the flavylium moiety into CB7 leads to a dramatic increase in the fluorescence quantum yield, from 0.29 in the free axle to 0.97 in the [2]pseudorotaxane and 1.0 in the [3]pseudorotaxane.
The molecular recognition of peptides and proteins by cucurbit[ n ]uril synthetic receptors in aqueous solution occurs with high affinity and with selectivity that is predictive from the sequence of amino acids and has enabled many applications.
Here we report the coupling of a cyclic peptide (VH4127) targeting the low density lipoprotein (LDL) receptor (LDLR) noncompetitively to cucurbit[7]uril (CB[7]) to develop a new kind of drug delivery system (DDS), namely, CB[7]-VH4127, with maintained binding affinity to the LDLR. To evaluate the uptake potential of this bismacrocyclic compound, another conjugate was prepared comprising a high-affinity group for CB[7] (adamantyl(Ada)-amine) coupled to the fluorescent tracker Alexa680 (A680). The resulting A680-Ada·CB[7]-VH4127 supramolecular complex demonstrated conserved LDLR-binding potential and improved LDLR-mediated endocytosis and intracellular accumulation potential in LDLR-expressing cells. The combination of two technologies, namely, monofunctionalized CB[7] and the VH4127 LDLR-targeting peptide, opens new avenues in terms of targeting and intracellular delivery to LDLR-expressing tissues or tumors. The versatile transport capacity of CB[7], known to bind a large spectrum of bioactive or functional compounds, makes this new DDS suitable for a wide range of therapeutic or imaging applications.
The binding interaction between 4-cyanophenol (4-CY) and cucurbit[7]uril has been studied using ¹H NMR spectroscopy, UV–vis absorption spectroscopy, fluorescence spectroscopy and X-ray crystallography. The corresponding absorption and emission spectra obtained in aqueous solution revealed that Q[7] and 4-CY formed a 1:1 host-guest type complex. A single crystal structure was obtained by introducing [ZnCl4]²⁻ and Ca²⁺ as structural inducers, which revealed that 4-CY was connected to Q[7] or [ZnCl4]²⁻ anion via weak interactions such as hydrogen bonding, C-H···π, ion-dipole, to afford a Q[7]-based supramolecular framework. Interestingly, the framework exhibited a Chinese knot-like structure.
The photoisomerization behavior of cyanostilbene molecules is a hotspot in supramolecular configuration transformation research. Here, we reported a cyanostilbene derivative that converted from the Z,Z-isomer to the E,E-isomer under UV light irradiation at 365 nm. This process can be reversibly converted only in the presence of cucurbit[8]uril under the same light source, accompanied by the reversible conversion of fluorescence from green to yellow. No effective configuration transformation occurred with guest molecules only or upon the addition of cucurbit[7]uril. The photoisomerization was fully characterized by UV-vis and fluorescence spectroscopy, NMR, high-resolution mass spectrometry, and transmission electron microscopy. This work provides a new method for the supramolecular macrocyclic-activated configuration transformation.
