Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• with the development of edelfosine (an anticancer drug). More recently, ohmline, a glyco glycero ether lipid that modulates selectively SK3 ion channels and reduces in vivo the occurrence of bone metastases, and other glyco glycero ether also identified as GAEL (glycosylated antitumor ether lipids

The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

• Marco Keller,
• Karl Sauvageot-Witzku,
• Franz Geisslinger,
• Nicole Urban,
• Michael Schaefer,
• Karin Bartel and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183

• relationships in this chemotype. Keywords: acyl Pictet–Spengler reaction; alkaloids; antiproliferative activity; benzyltetrahydroisoquinolines; ion channels; protective group; total synthesis; Introduction The benzylisoquinoline alkaloids are a large and diverse class of plant secondary metabolites including

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• exerted by fluoroprolines [108]. As a result, fluoroprolines could significantly impact the transition temperature in elastin-like sequences [108][109]. In ligand-gated ion channels, proline residues are involved in numerous loop positions as well as in the transmembrane helices, and the incorporation of

• incorporation on the enzymatic performance were characterized for a few enzymes [59][130][131][132][135] and the activity of ion channels [110][111][112][113]. These studies generally showed the preservation of the fold of the parent enzymes inferred from the preservation of their native activities. From these

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• accurate determination of inter-subunit distances in pentameric ligand-gated ion channels (pLGICs) by means of solution 19F PRE NMR experiments in micelles (Figure 13) [88]. To ensure a uniform 19F PRE signal from the adjacent paramagnetic labels, the 19F NMR TFET probe was tagged to a selected cysteine

• distance restraints for ion channels and other protein complexes that would be difficult to be defined by using other analytical tools. DNA and RNA secondary and tertiary structure 19F NMR spectroscopy also represents a useful analytical approach to study the structure, function and molecular dynamics of

Opening up connectivity between documents, structures and bioactivity

• Christopher Southan

Beilstein J. Org. Chem. 2020, 16, 596–606, doi:10.3762/bjoc.16.54

• followed by the IUPHAR Ion Channels Compendium of papers in 2003. This had developed into the IUPHAR-DB website by 2009 and was updated to the current IUPHAR/BPS Guide to Pharmacology (GtoPdb) by 2012 [10]. That same year also saw the first ChEMBL publication for which the website was live by 2010 [19

Chemical tuning of photoswitchable azobenzenes: a photopharmacological case study using nicotinic transmission

• Lorenzo Sansalone,
• Jun Zhao,
• Matthew T. Richers and
• Graham C. R. Ellis-Davies

Beilstein J. Org. Chem. 2019, 15, 2812–2821, doi:10.3762/bjoc.15.274

• into the corresponding cis configuration [1]. The reverse reaction can be initiated with a different wavelength. In a biological context, this photochromism was exploited first by Erlanger and colleagues for enzyme inhibitors in 1968 [2], and ion channels in 1971 [3]. Their ingenious approach was

• fundamentally different categories which were defined, historically, using pharmacology. The neurotransmitter-gated ion channels are activated by the drug nicotine, and these are called nicotinic (n)AChR. The G-protein-coupled receptors are activated by the drug muscarine, and these are called muscarinic (m

• . b) Structures of nicotinic acetylcholine receptor ligands. c) Illustration of how cis and trans agonists interact with ligand-gated ion channels. Supporting Information Supporting Information File 608: Additional figures, full synthetic details and NMR spectra, LC–MS of compounds 12 and 13 and LC

Photoreversible stretching of a BAPTA chelator marshalling Ca²⁺-binding in aqueous media

• Aurélien Ducrot,
• Arnaud Tron,
• Robin Bofinger,
• Ingrid Sanz Beguer,
• Jean-Luc Pozzo and
• Nathan D. McClenaghan

Beilstein J. Org. Chem. 2019, 15, 2801–2811, doi:10.3762/bjoc.15.273

• ions and switch between complexes of different molecularity, albeit largely in organic solvents [32]. Azobenzene is generally considered relatively resistant to fatigue and has been employed to evoke changes in different biological systems, including ion channels based on changes of properties between

A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

• Xavier Gómez-Santacana,
• Sabrina M. de Munnik,
• Tamara A. M. Mocking,
• Niels J. Hauwert,
• Shanliang Sun,
• Prashanna Vijayachandran,
• Iwan J. P. de Esch,
• Henry F. Vischer,
• Maikel Wijtmans and
• Rob Leurs

Beilstein J. Org. Chem. 2019, 15, 2509–2523, doi:10.3762/bjoc.15.244

• activity and physiological events with light. A number of protein targets have been explored with photochromic small-molecule ligands, such as ion channels, microtubules, enzymes and GPCRs (G protein-coupled receptors) [1][10]. We focus our photopharmacology research on GPCRs [3][7][11], which constitute a

Host–guest interactions between p-sulfonatocalix[4]arene and p-sulfonatothiacalix[4]arene and group IA, IIA and f-block metal cations: a DFT/SMD study

• Valya K. Nikolova,
• Cristina V. Kirkova,
• Silvia E. Angelova and
• Todor M. Dudev

Beilstein J. Org. Chem. 2019, 15, 1321–1330, doi:10.3762/bjoc.15.131

• , biopharmaceutical, biological, biomimetic (enzyme mimics, transport across membranes, ion channels, etc.) and biomedical (in cancer chemotherapy) applications, reviewed by Atwood et al. [15], Perret et al. [16], Da Silva et al. [17], Nimse et al. [18], Guo et al. [19], Agrawal et al. [20], Yousaf et al. [21]. The

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• increasingly become an attractive target over the past two decades [12][13][14]. PPIs are challenging targets because of their flat, large and hydrophobic binding surface, in comparison with the well-defined binding sites of more classical targets such as GPCRs, enzymes or ion channels (Figure 1). Moreover

Pd- and Cu-catalyzed approaches in the syntheses of new cholane aminoanthraquinone pincer-like ligands

• Nikolay V. Lukashev,
• Gennadii A. Grabovyi,
• Dmitry A. Erzunov,
• Alexey V. Kazantsev,
• Gennadij V. Latyshev,
• Alexei D. Averin and
• Irina P. Beletskaya.

Beilstein J. Org. Chem. 2017, 13, 564–570, doi:10.3762/bjoc.13.55

• arylaminocholanes and cholane-diaminoanthraquinone derivatives by Pd- and Cu-catalyzed amination. Such compounds not only have cation binding properties, but also might be easily introduced in lipid membranes to form ion channels. Appropriate close location of lipophilic steroid fragments in bis(cholanediamino

Self and directed assembly: people and molecules

• Tony D. James

Beilstein J. Org. Chem. 2016, 12, 391–405, doi:10.3762/bjoc.12.42

• least knowing how to) good research – summing up in Tom’s own words this was the “take home message from my PhD.” During my PhD we developed both self-assembling supramolecular pore formers as well as unimolecular ion channels for the transport of metal ions across biological membranes. The project

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• found to interact with hERG potassium ion channels resulting in a cardiac arrhythmia that can lead to fainting or even sudden death. In most of these cases this rare but severe side reaction cannot be tolerated and has therefore lead to drug failure in preclinical trials or even withdrawals of marketed

A chemist and biologist talk to each other about caged neurotransmitters

• Graham C.R. Ellis-Davies

Beilstein J. Org. Chem. 2013, 9, 64–73, doi:10.3762/bjoc.9.8

• transfers electrical signals between pre- and postsynaptic cells. Approximately 80% of such signaling is carried out by glutamate binding to AMPA receptors, the major post-synaptic excitatory ionotropic ion channels that bind glutamate. These receptors are blocked specifically by α-amino-3-hydroxy-5-methyl

• compounds do not block such receptors [40]. The effect of caged transmitters on other membrane receptors, such as voltage-caged ion channels, has not been well studied. The good news is that since the caged transmitters have a relatively low affinity for GABA-A receptors, it turns out that most, if not all

• a fairly straightforward task. Chemist: Since the discovery of the light-gated ion channels called channelrhodopsins (ChR) in 2002 [95] and 2003 [96], a second method for optical activation of neuronal cells has been developed. Some think that the massive and expanding popularity of optogenetic

Control over molecular motion using the cis–trans photoisomerization of the azo group

• Estíbaliz Merino and
• María Ribagorda

Beilstein J. Org. Chem. 2012, 8, 1071–1090, doi:10.3762/bjoc.8.119

• illumination, by means of the direct regulation of enzymatic activity [64][65][66][67], peptides, proteins, nucleic acids [68][69][70][71][72][73][74][75][76], receptors [77][78][79][80][81][82], or ion channels [83][84][85], or by modulation of the concentration of several labelled molecules. This strategy is

• , the cis isomer brings the aromatic rings closer, shortening its length, and hence the channel blocking is inefficient, allowing the passage of ions. The development of systems capable of photoregulating the activity of ion channels is extremely important in neurobiology. Recently, a maleimide

meta-Oligoazobiphenyls – synthesis via site-selective Mills reaction and photochemical properties

• Raphael Reuter and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2012, 8, 877–883, doi:10.3762/bjoc.8.99

• reduction of ~3.5 nm rendering it an ideal candidate for changing spatial arrangements on the molecular level. This change has been featured in a variety of applications [7][8][9], such as, switchable sensors [10], ion channels [11], catalysts [12], or liquid crystals [13]. In most of these applications

Planar-bilayer activities of linear oligoester bolaamphiphiles

• Jonathan K. W. Chui,
• Thomas M. Fyles and
• Horace Luong

Beilstein J. Org. Chem. 2011, 7, 1562–1569, doi:10.3762/bjoc.7.184

• voltage-dependent. The varied and irregular activities were summarized with the aid of a recently developed “activity-grid” method. Keywords: activity grid; single-molecule studies; synthetic ion channels; voltage clamp experiment; Introduction Ion channels modulate conductance in cell membranes, and

• ” of more complex systems. Since the pioneering report by Tabushi [5] some three decades ago, hundreds of disparate synthetic compounds have been shown to behave as ion channels, by ensemble and/or single-molecule techniques [6][7]. Ensemble techniques refer to the many variations of vesicle-based

• events indistinguishable from channels are possible [26]. It was recently reported that an applied potential can effect lipid phase transitions [27], one consequence of which is the creation of voltage-dependent lipid ion channels at the phase-transition temperature. Pure diphytanoyl phosphatidylcholine

The C–F bond as a conformational tool in organic and biological chemistry

• Luke Hunter

Beilstein J. Org. Chem. 2010, 6, No. 38, doi:10.3762/bjoc.6.38

• , including various (GABA)-gated ion channels and the metabolising enzyme GABA-aminotransferase. In order to rationally design drugs that are specific for individual GABA-binding proteins, it is necessary to know the conformation that the flexible molecule GABA adopts when binding that particular protein. One

Flexible synthesis of poison- frog alkaloids of the 5,8-disubstituted indolizidine- class. II: Synthesis of (-)-209B, (-)-231C, (-)-233D, (-)-235B", (-)-221I, and an epimer of 193E and pharmacological effects at neuronal nicotinic acetylcholine receptors

• Soushi Kobayashi,
• Naoki Toyooka,
• Dejun Zhou,
• Hiroshi Tsuneki,
• Tsutomu Wada,
• Toshiyasu Sasaoka,
• Hideki Sakai,
• Hideo Nemoto,
• H. Martin Garraffo,
• Thomas F. Spande and
• John W. Daly

Beilstein J. Org. Chem. 2007, 3, No. 30, doi:10.1186/1860-5397-3-30

• receptors are ligand-gated ion channels composed of five subunits. [4] To date, 12 nicotinic receptor subunits (α2-α10, β2-β4) have been identified. Subtypes of neuronal nicotinic receptors are constructed from numerous subunit combinations, which confer varied functional and pharmacological characteristics