Predictive recognition of native proteins by cucurbit[7]uril in a complex mixture

179

Cucurbit[7]uril (CB[7]) and cucurbit[8]uril (CB[8]) are two key members of the cucurbit[n]uril (CB[n]) family of macrocycles. Because of the good water solubility of CB[7] and the unique ternary binding properties of CB[8], these two macrocycles have attracted increasing attentions in recent years. In particular, many promising reports of exciting applications regarding CB[7] and CB[8] have emerged in the pharmaceutical sciences and complexations of biomolecules, which has become one of the most important areas of potential applications of CB[n]s. This review summarizes the applications of macrocyclic CB[7], CB[8] and their derivatives as supramolecular platforms that have been developed in recent years within the field of pharmaceutical sciences and biomolecular sciences, and discusses the current challenges and future prospects of this area.

Section: Complexations Of Biomolecules and Their Biomedical Implicationsmentioning

confidence: 99%

Applications of Cucurbit[n]urils (n=7 or 8) in Pharmaceutical Sciences and Complexation of Biomolecules

Yin

Wang

2017

179

“…Glycoluril hexamer has been used as a versatile building block for the preparation of monofunctionalized derivatives of CB[6] and CB[7]. [20] …”

Section: Acyclic Cb[n]-type Receptorsmentioning

confidence: 99%

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

Ganapati

Isaacs

2017

Self Cite

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.

“…308 (De À11) [136] penicillin G antibiotic [136] somatostatin growth hormone-inhibiting hormone 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 Table 3. [208] FGGÀEra-14-3-3b…”

Section: Cbn Based System [A]mentioning

confidence: 99%

Chemical Sensors Based on Cucurbit[n]uril Macrocycles

Sinn

Biedermann

2018

147

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.