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Isothermal titration calorimetry data for (a) titration of 80 μM CB8 with 1.5 mM of NVoc-FGG in neutral water and for (b) 120 μM CB8 titrated with 3.0 mM of FGG in neutral water.
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...
Contexts in source publication
Context 1
... Importantly, in our approach, the strong association of NVoc-FGG with CB8 assures the spatial colocalization of the macrocycle and the FGG prior to light stimulation. Direct proof for the binding of NVoc-FGG by CB8 was obtained from isothermal titration experiments (ITC); see Figure 1. The ITC data are compatible with 1:1 binding as seen from the inflection of the titration curve at ∼1 equiv of titrant. ...
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... latter does not bind to CB8 with a significant affinity; no heat release was seen in the ITC experiment, and also no significant changes were observed in the UV/vis absorption spectrum of NVoc-Phe in the presence of CB8 (see Figures S12 and S13 in the Supporting Information). Noteworthy, Phe binds with a homoternary binding constant 4 orders of magnitude lower than that of FGG (K 11 K 12 = 5.0 × 10 8 M −2 for Phe; see Figure S13 in the Supporting Information). This underpins the stabilizing role of the glycine rests in FGG, as visualized in a previously reported crystal structure, 17 showing dipole−dipole interactions of the amide NHs with receptor portal carbonyl groups. ...
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... addition of CB8 to the NVoc-FGG ligand, new 1 H NMR signals, assigned to the complex, appear in slow exchange with those of the free ligand. The titration data and the complete assignment of the signals can be found in the Supporting Information (Figures S15−S17). Reaching 1 equiv of CB8, the signals of the free ligand completely disappear and no further changes are observed upon addition of excess CB8. ...
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... is in accordance with the formation of a stable 1:1 complex. Noteworthy, the assembly also shows several signals under chemical exchange, which were assigned to two rotamers arising from the slow rotation around the N−C carbamate (N−CO) bond ( Figure S14); see Supporting Information for a detailed discussion. The 1 H NMR signals of the phenylalanine part and NVoc groups appear significantly shifted to higher field, in agreement with the concomitant inclusion of the two moieties in the receptor cavity. ...
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... proton signals of the NVoc methoxy groups are shifted to lower field, indicating their localization near the CB8 carbonyl portals. The 1 H NMR titration of FGG with CB8 (see Figure S18 in the Supporting Information) is in line with the previously established formation of a homoternary complex. 17 The formation of higher-order 2:2 (or n/n) receptor−ligand complexes with CB8 has been recently identified as a potential pitfall in the analysis of such systems, which may lead to the erroneous assignment of a 1:1 binding stoichiometry. ...
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... The formation of higher-order 2:2 (or n/n) receptor−ligand complexes with CB8 has been recently identified as a potential pitfall in the analysis of such systems, which may lead to the erroneous assignment of a 1:1 binding stoichiometry. 64 In order to discard this possibility in the case of the NVoc-FGG@ CB8 complex, we rely on a DOSY experiment (see Figures S19 and S20 in the Supporting Information). This afforded a diffusion coefficient of D obs = 2.9 × 10 −10 m 2 s −1 , which is in agreement with a 1:1 binding stoichiometry. ...
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... Having the transformation from 1:1 to 2:1 binding stoichiometry on changing from NVoc-FGG to FGG unambiguously established, we proceeded to demonstrate the light-induced supramolecular dimerization of FGG. The light irradiation (366 nm) of a solution of NVoc-FGG in the absence or presence of CB8 (1.4 equiv) yields UV/vis spectral variations (observed for the NVoc-derived photoproduct buildup at 415 nm) that are compatible with the removal of the NVoc group from the FGG tripeptide (see Figures S21 and S22 in the Supporting Information). It can be safely assumed that the mechanism of the photoreaction follows the same path as that derived from detailed transient absorption studies of related NVoc derivatives. ...
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.
