Rational design and implementation of a cucurbit[8]uril-based indicator-displacement assay for application in blood serum

Chemical Science
Stephan SinnFrank Biedermann

Abstract

In this study, we report the first supramolecular indicator-displacement assay (IDA) based on cucurbit[n]uril (CBn) hosts that is operational in blood serum. Rational design principles for host-guest chemosensing in competitively binding media were derived through detailed mathematical simulations. It was shown that currently known CBn-based chemosensing ensembles are not suited for use in highly competitive matrices such as blood serum. Conversely, the simulations indicated that a combination of cucurbit[8]uril (CB8) and an ultra-high affinity dye would be a promising IDA reporter pair for the detection of Alzheimer's drug memantine in blood serum. Therefore, a novel class of [2.2]paracyclophane-derived indicator dyes for the host CB8 was developed that possesses one of the highest host-guest affinities (Ka > 1012 M-1 in water) known in supramolecular host-guest chemistry, and which provides a large Stokes shift (up to 200 nm). The novel IDA was then tested for the detection of memantine in blood serum in a physiologically relevant sub- to low micromolar concentration range.

References

Aug 5, 1997·Chemical Reviews·A. Prasanna de SilvaTerence E. Rice
Feb 6, 2003·Journal of the American Chemical Society·Huarui HeJames K Tusa
Apr 15, 2004·Analytical Biochemistry·Andrew W DrakeScott L Klakamp
Jul 30, 2005·Angewandte Chemie·Jason LagonaLyle Isaacs
Nov 10, 2005·Journal of the American Chemical Society·Simin LiuLyle Isaacs
Dec 22, 2005·Current Opinion in Pharmacology·Jon W Johnson, Shawn E Kotermanski
Oct 26, 2006·Journal of the American Chemical Society·Pritam MukhopadhyayLyle Isaacs
Mar 21, 2007·Molecular BioSystems·Thomas Schrader, Sebastian Koch
Mar 30, 2007·Organic Letters·Tianzhi Zhang, Eric V Anslyn
Jun 29, 2007·Clinical Pharmacokinetics·Johannes KornhuberIngolf Meineke
Aug 19, 2007·Angewandte Chemie·Grigory V ZyryanovPavel Anzenbacher
Sep 26, 2007·Current Medical Research and Opinion·Gary Small, Bruno Dubois
Jan 17, 2008·Chemical Society Reviews·Hans-Jörg Schneider, Anatoly K Yatsimirsky
Mar 24, 2009·Current Neuropharmacology·G RammesC G Parsons
Nov 26, 2009·Chemistry : a European Journal·Sébastien RochatKay Severin
Jan 22, 2011·Chemistry, an Asian Journal·Young Ho KoKimoon Kim
Apr 9, 2011·Journal of the American Chemical Society·Jordan M ChinaiAdam R Urbach
Apr 26, 2011·Journal of the American Chemical Society·Garima GhaleWerner M Nau
Mar 1, 2012·Chemistry : a European Journal·Roy N DsouzaWerner M Nau
Mar 14, 2012·Journal of Pharmaceutical and Biomedical Analysis·Muriel NoetzliChin B Eap
Feb 21, 2013·Nature Chemistry·David BierChristian Ottmann
May 16, 2013·American Journal of Epidemiology·Ian J BrownUNKNOWN INTERSALT Co-Operative Research Group
May 25, 2013·Chemical Society Reviews·Hans-Jörg SchneiderAnatoly K Yatsimirsky
Sep 5, 2013·Journal of the American Chemical Society·Tsuyoshi MinamiPavel Anzenbacher
Sep 14, 2013·Angewandte Chemie·Otto S Wolfbeis
Jan 3, 2014·Angewandte Chemie·Liping CaoLyle Isaacs
Jun 4, 2014·Journal of the American Chemical Society·Seán T J RyanOren A Scherman
Aug 20, 2014·Physical Chemistry Chemical Physics : PCCP·Zsombor Miskolczy, László Biczók
Oct 16, 2014·Chemical Society Reviews·Khaleel I Assaf, Werner M Nau
Nov 29, 2014·Angewandte Chemie·Amir NorouzyWerner M Nau
Feb 27, 2015·Chemical Reviews·Lei YouEric V Anslyn
Nov 14, 2015·Chemical Reviews·Steven J BarrowOren A Scherman
Sep 28, 2016·Journal of the American Chemical Society·Alexandra I LazarWerner M Nau
Dec 22, 2016·Journal of the American Chemical Society·Andrew T BockusAdam R Urbach
Feb 10, 2017·Journal of the American Chemical Society·David SigwaltLyle Isaacs
Feb 14, 2017·Chemical Society Reviews·Wenqi LiuLyle Isaacs
Jun 14, 2017·Journal of the American Chemical Society·Li-Li WangWei Jiang
Aug 3, 2017·Chemical Communications : Chem Comm·Gyan H AryalLiming Huang
Mar 6, 2018·Chemical Communications : Chem Comm·Kohei YazakiMichito Yoshizawa

❮ Previous
Next ❯

Citations

Mar 4, 2020·Chemical Communications : Chem Comm·Patricia RemónUwe Pischel
Mar 21, 2020·Chemical Communications : Chem Comm·Adam D GillRichard J Hooley
Jan 17, 2020·Chemistry : a European Journal·László BiczókFrank Biedermann
May 28, 2020·Chemical Communications : Chem Comm·Stephan SinnFrank Biedermann
Aug 1, 2020·Chemistry : a European Journal·Anxun ZhengCheuk-Fai Chow
Nov 8, 2019·Chemical Communications : Chem Comm·Shuai ZhangWerner M Nau
Sep 19, 2020·Chemical Communications : Chem Comm·Amrutha PrabodhFrank Biedermann
Jun 2, 2021·The Journal of Organic Chemistry·Rita J FernandesNuno Basílio
Jun 19, 2021·Organic & Biomolecular Chemistry·Ishfaq Ahmad Rather, Rashid Ali
Aug 6, 2021·Chemical Science·Amrutha PrabodhFrank Biedermann
Sep 5, 2020·Journal of the American Chemical Society·Huang WuJ Fraser Stoddart
Dec 1, 2021·Chemical Communications : Chem Comm·Madushani DharmarwardanaBradley D Smith

❮ Previous
Next ❯

Methods Mentioned

BETA
Fluorescence
NMR
column chromatography

Software Mentioned

Wolfram Mathematica
G16

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.