Recognition Properties of Acyclic Glycoluril Oligomers

Lucas, Derick; Isaacs, Lyle

doi:10.1021/ol201636q

Cited by 27 publications

(19 citation statements)

References 52 publications

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“…[21] Hosts 15 and 16 display slow kinetics of exchange on the chemical shift timescale for guests HDA and PXDA despite the acyclic nature of the host. Table 1 presents the measured binding constants toward 14 – 16 and also toward CB[6] and CB[7].…”

Section: Acyclic Cb[n]-type Receptorsmentioning

confidence: 99%

Acyclic Cucurbit[n]uril‐type Receptors: Preparation, Molecular Recognition Properties and Biological Applications

Ganapati

Isaacs

2017

Israel Journal of Chemistry

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This article traces the development of acyclic cucurbit[n]uril-type receptors with a focus on work from the Isaacs group. First, we describe the synthesis of methylene bridged glycoluril dimers capped with aromatic sidewalls which allowed us to probe the interconversion of the S- and C-shaped dimers which is a fundamental step in CB[n] formation. The C-shaped compounds were found to undergo discrete self-assembly (dimerization) in both water and organic solvents which lead us to investigate multicomponent self-sorting systems. We supressed the self-association of by electrostatic repulsion in the putative dimer which allowed expression of its innate molecular recognition properties toward methylene blue and related planar cationic dyes. Longer glycoluril oligomers (trimer - hexamer, acyclic decamer) were prepared by starving the CB[n]-forming reaction of formaldehyde. The longer oligomers (e.g. and ) bind to alkylammonium ions in water ≈ 100-fold weaker than macrocyclic CB[n] highlighting the high preorganization of the acyclic but polycyclic framework. We prepared a wide variety of acyclic CB[n] compounds (wall variants, solubilizing group variants, linker variants) based on glycoluril trimer and tetramer. In particular, and have been shown to possess a wide variety of chemically and biologically interesting functions. For example, was used to formulate the insoluble drug Albendazole and treat mice bearing SK-OV-3 xenograft tumors. Compound binds tightly to the neuromuscular blocking agents rocuronium, vecuronium, and cisatracurium and acts as an reversal agent for these compounds in anesthetized rats. Container was also found to modulate the hyperlocomotive effect of rats that had been treated with methamphetamine. Finally, has been used as a cross reactive component of sensor arrays that are capable of classifying and quantifying cancer related nitroamines and a range of over the counter drugs. Overall, the work demonstrates that acyclic CB[n]-type compounds are nicely pre-organized and therefore retain the essential aspects of the recognition properties of macrocyclic CB[n] but allow for more straightforward tailoring of structure and solubility that enables a variety of chemically and biologically important applications.

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Section: Acyclic Cb[n]-type Receptorsmentioning

confidence: 99%

Acyclic Cucurbit[n]uril‐type Receptors: Preparation, Molecular Recognition Properties and Biological Applications

Ganapati

Isaacs

2017

Israel Journal of Chemistry

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“…[11][12][13] Numerous Qn homologues, 14,15 derivatives, [16][17][18][19][20] and acyclic congeners 21 have extended the family to myriad structures and applications. 22 Q8 and its homologue cucurbit [7]uril (Q7) have been shown to bind amino acids, peptides, and proteins, with preference for the aromatic residues tryptophan (Trp), phenylalanine (Phe), and tyrosine (Tyr), especially when located at the N-terminal position in the polypeptide chain.…”

Section: Introductionmentioning

confidence: 99%

Sequence-Specific, Nanomolar Peptide Binding via Cucurbit[8]uril-Induced Folding and Inclusion of Neighboring Side Chains

et al. 2015

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This paper describes the molecular recognition of the tripeptide Tyr-Leu-Ala by the synthetic receptor cucurbit[8]uril (Q8) in aqueous buffer, with nanomolar affinity, and with exceptional specificity. This combination of characteristics, which also applies to antibodies, is desirable for applications in biochemistry and biotechnology but has eluded supramolecular chemists for decades. Building on prior knowledge that Q8 binds to peptides with N-terminal aromatic residues, a library screen of 105 peptides was designed to test the effects of residues adjacent to N-terminal Trp, Phe, or Tyr. The screen used tetramethylbenzobis(imidazolium) (MBBI) as a fluorescent indicator and resulted in the unexpected discovery that MBBI can serve not only as a turn-off sensor via the simultaneous inclusion of a Trp residue, but also as a turn-on sensor via the competitive displacement of MBBI upon binding of Phe-or Tyr-terminated peptides. The unusual fluorescence response of the Tyr series prompted further investigation by 1 H NMR spectroscopy, electrospray ionization mass spectrometry, and isothermal titration calorimetry. From these studies, a novel binding motif was discovered in which only one equivalent of peptide binds to Q8, and the sidechains of both the N-terminal Tyr residue and its immediate neighbor bind within the Q8 cavity. For the peptide Tyr-Leu-Ala, the equilibrium dissociation constant value is 7.2 nM, whereas that of its sequence isomer Tyr-Ala-Leu is 34 M. The high stability, recyclability, and low cost of Q8 combined with the straightforward incorporation of Tyr-Leu-Ala into recombinant proteins should make this system attractive for the development of biological applications.

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“…[73,74,75] Finally, despite their chemical inertness, there are pathways with which CBn macrocycles can be functionalized, e. g., via a step-wise builtup of functionalised CBn derivatives from tailor-made monomers, or via controlled oxidative hydroxylation of CBn macrocycles. [32,36,66,87,88,89,90,91] The CBn-functionalization opportunities also open the path to practically preferred immobilised chemosensors. [32,36,66,87,88,89,90,91] The CBn-functionalization opportunities also open the path to practically preferred immobilised chemosensors.…”

Section: Analytementioning

confidence: 99%

“…[22,32,36,66,88,89,90,91,113,114] On account of their open, deformable structure, also analytes that cannot be immersed into the cavities of cyclic CBn hosts can be bound by the acyclic CBn counterparts, e. g., carbon nanotubes. [22,32,36,66,88,89,90,91,113,114] On account of their open, deformable structure, also analytes that cannot be immersed into the cavities of cyclic CBn hosts can be bound by the acyclic CBn counterparts, e. g., carbon nanotubes.…”

Section: Selection Criteria For Choosing a Cbn Component As The Analymentioning

confidence: 99%

Chemical Sensors Based on Cucurbit[n]uril Macrocycles

Sinn

Biedermann

2018

Israel Journal of Chemistry

147

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Cucurbit[n]urils (CBn) are glycoluril‐based macrocyclic hosts that bind many biologically, medicinally and environmentally relevant analytes with record high affinities in aqueous media. They are therefore prime candidates for the design of chemosensors that are operational in biological fluids, waste and drinking water and have promising potential to be utilized for in vitro and in vivo sensing and imaging applications. Unlike protein‐based antibodies, CBn can be prepared in multi kilogram scales, they are chemically robust and they show a desired fast analyte‐binding kinetics. Unlike protein‐based antibodies, CBn can be prepared in multi kilogram scales, are chemically robust and show a desired fast analyte‐binding kinetics Selective analyte detection and differentiation is possible owing to the charge‐ and size‐selective binding characteristics of the CBn members and due to the wide range of cyclic and acyclic CBn derivatives that differ in their analyte binding preference. Because CBn hosts are spectroscopically silent in the visible electromagnetic spectrum, optical signal transduction with CBn based chemosensing ensembles is typically performed by indicator displacement assays (IDA), which are easy to implement and applicable to both aliphatic and aromatic analytes. The extension to array‐based sensing with CBn chemosensors is straightforward. Associative binding assays (ABA), which are uniquely available with CB8‐based self‐assembled receptors offer superior analyte differentiation possibility due to emerging spectral fingerprints in the absorbance, circular dichroism (CD) and emission spectra for the receptor•analyte complexes. Direct signal generation is promising for inherently spectroscopically active analytes, for instance through absorbance, CD, emission and surface enhanced Raman spectroscopy (SERS). Sensitive NMR (19F, 129Xe) techniques, electron spin resonance (ESR), redox, and mass spectrometry are also valuable signal transduction options for specific analytes. CBn based chemosensors were successfully utilized for the monitoring of biophysical processes and enzymatic reactions with label free analytes or substrates in real time. These applications capitalize on the fast equilibration kinetics of CBn‐analyte complexes and the bio‐compatibility of CBn hosts. The tabulated large body of data extracted from reported CBn‐based binding studies is hoped to provide the reader with a valuable starting point for designing practically applicable CBn‐based sensors.

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Recognition Properties of Acyclic Glycoluril Oligomers

Cited by 27 publications

References 52 publications

Acyclic Cucurbit[n]uril‐type Receptors: Preparation, Molecular Recognition Properties and Biological Applications

Acyclic Cucurbit[n]uril‐type Receptors: Preparation, Molecular Recognition Properties and Biological Applications

Sequence-Specific, Nanomolar Peptide Binding via Cucurbit[8]uril-Induced Folding and Inclusion of Neighboring Side Chains

Chemical Sensors Based on Cucurbit[n]uril Macrocycles

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