Covalent cucurbit[7]uril–dye conjugates for sensing in aqueous saline media and biofluids

Hu, Chang‐Ming; Grimm, Laura; Prabodh, Amrutha; Baksi, Ananya; Siennicka, Alicja; Levkin, Pavel A.; Kappes, Manfred M.; Biedermann, Frank

doi:10.1039/d0sc03079a

Cited by 46 publications

(46 citation statements)

References 94 publications

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“…Harnessing the noncovalent nature of analyte/ chemosensor binding, these supramolecular host−guest systems are especially used in indicator displacement assays (IDA) 28 that combine the host−guest supramolecular interaction and fluorescence signaling in one system for sensing. 24,27,29,30 Here, displacement of an environment responsive indicator dye from a host/receptor by the analyte is accompanied by readily measurable changes in the emission properties (e.g., intensity or wavelength).…”

Section: ■ Introductionmentioning

confidence: 99%

Cucurbit[n]uril-Immobilized Sensor Arrays for Indicator-Displacement Assays of Small Bioactive Metabolites

Zhong

Kumar

et al. 2021

ACS Appl. Nano Mater.

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The patterned immobilization of chemosensors into nano/microarrays has often boosted utilization in diagnostics and environmental sensing applications. While this is a standard approach for biosensors, e.g., with antibodies, other proteins, and DNA, arraying is not yet adopted widely for supramolecular chemosensors which are still predominantly used in solution systems. Here we introduce the patterned immobilization of cucurbit[n]urils (CBn) into multiplexed microarrays and elucidate their prospects for the advancement of surface-bound indicator-displacement assays to detect small molecule analytes. The microarrays were generated by microchannel cantilever spotting of functionalized CBn and subsequent self-assembly of the corresponding indicator dyes from solution. Enhanced sensitivity of surface-bound microarrays was established in demonstrations with small bioactive metabolites (spermine, amantadine, and cadaverine) compared to bulk assays. Furthermore, the integration of the CBn/indicator microarrays into microfluidic channels provides an efficient route for real-time monitoring of the sensing process, allows easier handling, and reduces need for analyte volume. The concept was further extended to differential sensing of analytes on diplex or multiplex CBn/indicator microarrays, opening up a route for multicomponent sensing of small molecule analytes in complex liquids.

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Section: ■ Introductionmentioning

confidence: 99%

Cucurbit[n]uril-Immobilized Sensor Arrays for Indicator-Displacement Assays of Small Bioactive Metabolites

Zhong

Kumar

et al. 2021

ACS Appl. Nano Mater.

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“…Supramolecular PEGylation using macrocyclic host–guest interactions thus presents an attractive alternative. , One particular macrocycle, cucurbit[7]uril (CB[7]), has been proven especially useful for such applications due to its broad range of affinity in binding a variety of different guest chemistries and high water solubility relative to other macrocycles in the CB[ n ] class. − Complexation of CB[7] and guests has been estimated to occur with dynamics near the diffusion limit, although guest binding is slowed slightly in the presence of cations ( e.g. , Na + in serum) due to competition from portal interactions between the cation and CB[7]. − The association rate under physiological conditions can therefore reasonably be approximated as k on ∼ 10 7 M –1 s –1 , − with changes in guest binding affinity ( K eq ), thus enabling direct control over the exchange rate ( k off ) of the interaction. The N-terminal (B1) phenylalanine on insulin has been identified as a guest molecule for CB[7] binding ( K eq = 1.5 × 10 6 M –1 ) .…”

Section: Introductionmentioning

confidence: 99%

Affinity-Directed Dynamics of Host–Guest Motifs for Pharmacokinetic Modulation via Supramolecular PEGylation

et al. 2021

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Proteins are an impactful class of therapeutics but can exhibit suboptimal therapeutic performance, arising from poor control over the timescale of clearance. Covalent PEGylation is one established strategy to extend circulation time but often at the cost of reduced activity and increased immunogenicity. Supramolecular PEGylation may afford similar benefits without necessitating that the protein be permanently modified with a polymer. Here, we show that insulin pharmacokinetics can be modulated by tuning the affinity-directed dynamics of a host–guest motif used to non-covalently endow insulin with a poly(ethylene glycol) (PEG) chain. When administered subcutaneously, supramolecular PEGylation with higher binding affinities extends the time of total insulin exposure systemically. Pharmacokinetic modeling reveals that the extension in the duration of exposure arises specifically from decreased absorption from the subcutaneous depot governed directly by the affinity and dynamics of host–guest exchange. The lifetime of the supramolecular interaction thus dictates the rate of absorption, with negligible impact attributed to association of the PEG upon rapid dilution of the supramolecular complex in circulation. This modular approach to supramolecular PEGylation offers a powerful tool to tune protein pharmacokinetics in response to the needs of different disease applications.

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“…S2-S4) through nucleophilic substitution reaction. 27 AIECB [7] was synthesized via CuAAC-catalyzed "click" reaction between CB[7]-alkyne and an azido functionalized fluorescence AIEgen photosensitizer (TPEPy-N 3 , Fig. S5-S11).…”

Section: Resultsmentioning

confidence: 99%

Synthesis of an AIEgen functionalized cucurbit[7]uril for subcellular bioimaging and synergistic photodynamic therapy and supramolecular chemotherapy

Chen

Wang

et al. 2021

Chem. Sci.

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Covalent cucurbit[7]uril–dye conjugates for sensing in aqueous saline media and biofluids

Abstract: Non-covalent chemosensing ensembles of cucurbit[n]urils (CBn) have been widely used in proof-of-concept sensing applications, but they are prone to disintegrate in saline media, e.g. biological fluids. We show here that...

Cited by 46 publications

References 94 publications

Cucurbit[n]uril-Immobilized Sensor Arrays for Indicator-Displacement Assays of Small Bioactive Metabolites

Cucurbit[n]uril-Immobilized Sensor Arrays for Indicator-Displacement Assays of Small Bioactive Metabolites

Affinity-Directed Dynamics of Host–Guest Motifs for Pharmacokinetic Modulation via Supramolecular PEGylation

Synthesis of an AIEgen functionalized cucurbit[7]uril for subcellular bioimaging and synergistic photodynamic therapy and supramolecular chemotherapy

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