Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• potential of compounds [43]. To assess the specific uptake of the G-3 aptamer, we used TZM-bLs. TZM-bL is a HeLa-derived cell line that was engineered to express CD4 and CCR5 receptors on the cell surface [44]. HeLa cells were used as a negative control. To investigate the specific uptake of the A-1 aptamer

• complexation with cluster of differentiation 4 (CD4) and CCR5 or C-X-C motif chemokine receptor 4 (CXCR4) host cell surface receptors [35]. As such, gp160 expression on the host cell surface receptor may not be as adept at facilitating cell entry via receptor-mediated endocytosis. Although in 2009, Zhou et al

• also be due to differences in target receptor expression in the cell types and/or differences in the affinity and specificity of these aptamers for the target receptors and/or differences in the mechanisms of uptake. Finally, the formulation procedure also likely influences the ability of the aptamers

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

• Maryna O. Mazur,
• Oleksii S. Zhelavskyi,
• Eugene M. Zviagin,
• Svitlana V. Shishkina,
• Vladimir I. Musatov,
• Maksim A. Kolosov,
• Elena H. Shvets,
• Anna Yu. Andryushchenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2021, 17, 678–687, doi:10.3762/bjoc.17.57

• of 1,2,4-triazolobenzodiazepines is the treatment of central nervous system (CNS) disorders. Such drugs as alprazolam and estazolam are used as anxiolytic agents, whereas adinazolam is known as an antidepressant [3]. Benzodiazepine molecules are ligands for GABA-receptors and act as positive

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• 6-O-analogues are less common [61]. Azolylpurine derivatives are important due to their potential as drug candidates. They can be used as agonists and antagonists of adenosine receptors [58][64][65][66] and against Mycobacterium tuberculosis [60]. They also show useful fluorescent properties [11][67

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• activity against Mycobacterium tuberculosis and also as agonists and antagonists of adenosine receptors [18]. In 2013, we developed an efficient approach for the synthesis of ribo- and arabino-2,6-bistriazolylpurine nucleosides and showed that the triazolyl ring in the C6 position of purine acts as a good

Supramolecular polymerization of sulfated dendritic peptide amphiphiles into multivalent L-selectin binders

• David Straßburger,
• Svenja Herziger,
• Katharina Huth,
• Moritz Urschbach,
• Rainer Haag and
• Pol Besenius

Beilstein J. Org. Chem. 2021, 17, 97–104, doi:10.3762/bjoc.17.10

• achieved. As specific biological interactions strongly rely on the receptor–ligand interplays, we are interested in investigating the targeting of isolated receptors by supramolecular polymers built from peptide amphiphiles decorated with suitable ligand structures. The well-known L-selectin described

Chiral anion recognition using calix[4]arene-based ureido receptors in a 1,3-alternate conformation

• Tereza Horáčková,
• Jan Budka,
• Vaclav Eigner,
• Wen-Sheng Chung,
• Petra Cuřínová and
• Pavel Lhoták

Beilstein J. Org. Chem. 2020, 16, 2999–3007, doi:10.3762/bjoc.16.249

• of calix[4]arene immobilised in the 1,3-alternate conformation led to a system possessing a preorganised ureido cavity hemmed with chiral alkyl units in the near proximity. As shown by the 1H NMR titration experiments, these compounds can be used as receptors for chiral anions in DMSO-d6. The chiral

• for N-acetyl-ʟ-phenylalaninate. The structures of some receptors were confirmed by single crystal X-ray analysis. Keywords: anion recognition; calixarene; chiral receptor; complexation; enantiodiscrimination; Introduction The recognition and complexation of anions has become undoubtedly one of the

• have gradually been revealed and are well recognised to date. Consequently, given the importance of anions in many areas of everyday life, including, e.g., biology, medicine, environmental pollution issues, or industrial processes, the design and development of novel artificial receptors/sensors for

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• fluorescence techniques have attracted immense interest. Synthetic peptide-based fluorescent probes are advantageous over protein-based sensors, since they are synthetically accessible, more stable, and can be easily modified in a site-specific manner for selective biological applications. Peptide receptors

• -aminobutyric acid associate with membrane-bound protein receptors and trigger changes in receptor shape and activity with subsequent signaling across the membrane. Noncovalent H-bonding and van der Waals interactions are the basis for the selective molecular recognition between a G-coupled protein receptor and

• a bound glutamate molecule [4]. Peptides often work as signaling molecules or hormones, such as small neuropetide endorphins, produced by the central nervous system to relieve stress or enhance pleasure. They produce signaling cascades in the brain by interacting with opiate receptors. Sometimes

UV resonance Raman spectroscopy of the supramolecular ligand guanidiniocarbonyl indole (GCI) with 244 nm laser excitation

• Tim Holtum,
• Vikas Kumar,
• Daniel Sebena,
• Jens Voskuhl and
• Sebastian Schlücker

Beilstein J. Org. Chem. 2020, 16, 2911–2919, doi:10.3762/bjoc.16.240

• -covalent interactions namely hydrogen bonds, van der Waals, and/or hydrophobic interactions [1][2][3][4][5]. In this context, Schmuck and co-workers have introduced a class of synthetic receptors based on the guanidiniocarbonyl pyrrole (GCP) moiety (cf. Figure 1 top right) as a carboxylate binding site

• supramolecular ligands: guanidiniocarbonyl pyrrole (GCP) and guanidiniocarbonyl indole (GCI). The latter class of artificial carboxylate receptors is a potential next generation binder based on the GCI motif which maintains the good carboxylate binding properties of GCP. GCI comprises an indole ring instead of a

• receptor. The vibrational assignment of these modes is important for the binding study of GCI receptors because we hypothesize that they are all involved in the complexation with carboxylates. Finally, we employed UVRR spectroscopy at 244 nm excitation to observe the binding events of GCI-based receptors

Encrypting messages with artificial bacterial receptors

• Pragati Kishore Prasad,
• Naama Lahav-Mankovski,
• Leila Motiei and
• David Margulies

Beilstein J. Org. Chem. 2020, 16, 2749–2756, doi:10.3762/bjoc.16.225

• receptors is described. We show that the binding of DNA-based artificial receptors to E. coli expressing His-tagged outer membrane protein C (His-OmpC) induces a Förster resonance energy transfer (FRET) between the dyes, which results in the generation of a unique fluorescence fingerprint. Because the

• information protection at the molecular level. Keywords: artificial receptors; cell surface modification; fluorescent probes; molecular cryptography; Introduction In living cells, information is processed and transferred via a series of recognition and signaling events, which normally begin by the binding

• of cell-surface receptors to extracellular signals, such as small molecules or proteins. In recent years, there has been considerable interest in modifying cells with artificial receptors, as a means to provide them with new properties [1]. We have recently reported a method for decorating His-tagged

Selective recognition of ATP by multivalent nano-assemblies of bisimidazolium amphiphiles through “turn-on” fluorescence response

• Rakesh Biswas,
• Surya Ghosh,
• Shubhra Kanti Bhaumik and
• Supratim Banerjee

Beilstein J. Org. Chem. 2020, 16, 2728–2738, doi:10.3762/bjoc.16.223

• Rakesh Biswas Surya Ghosh Shubhra Kanti Bhaumik Supratim Banerjee Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur-741246, Nadia, India 10.3762/bjoc.16.223 Abstract Bisimidazolium receptors, tagged with chromophoric pyrene at one end and linked

• the receptor with their complementary binding partners in the target analyte [15]. One of the ways to design multivalent systems is to connect the receptors through covalent linkages. Conjugated polymers and conjugated polymer electrolytes are prominent examples of covalently constructed multivalent

• [36][37][38], conjugated polymers [39][40][41][42], quantum dots [43][44] and sensors based on organic receptors such as imidazolium, ammonium, guanidinium [45][46][47][48][49][50][51][52], etc. have also been developed. Imidazolium based synthetic receptors typically utilize a combination of

Optical detection of di- and triphosphate anions with mixed monolayer-protected gold nanoparticles containing zinc(II)–dipicolylamine complexes

• Lena Reinke,
• Julia Bartl,
• Marcus Koch and
• Stefan Kubik

Beilstein J. Org. Chem. 2020, 16, 2687–2700, doi:10.3762/bjoc.16.219

• other serves to dilute the receptor units on the surface to such an extent that analyte binding to units residing on the same nanoparticle becomes unlikely. The number of receptors should still be high enough to allow nanoparticle crosslinking to benefit from multivalent interactions [19][20][21]. The

• solution, potentially giving rise to highly selective receptors if the two binding sites are arranged at a distance that allows for binding a diphosphate, but not a larger triphosphate anion. The peptide and cyclopeptide-derived receptors introduced by Jolliffe are examples [26] along with a range of

• receptors based on other scaffolds [22][23][24][25]. To test whether this binding motif induces AuNP crosslinking, we synthesized nanoparticles containing peripheral zinc(II)–DPA complexes together with a solubilizing triethylene glycol-based ligand in different ratios and studied their interaction with

Thermodynamic and electrochemical study of tailor-made crown ethers for redox-switchable (pseudo)rotaxanes

• Henrik Hupatz,
• Marius Gaedke,
• Hendrik V. Schröder,
• Julia Beerhues,
• Arto Valkonen,
• Fabian Klautzsch,
• Sebastian Müller,
• Felix Witte,
• Kari Rissanen,
• Biprajit Sarkar and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2020, 16, 2576–2588, doi:10.3762/bjoc.16.209

• made towards switchable macrocyclic receptors, in which crown ethers are functionalized with a stimuli-responsive unit [14][15]. These studies were mainly motivated by a biomimetic approach and included examples such as crown ethers incorporating photo-responsive azobenzene [15][16] or redox-active

Water-soluble host–guest complexes between fullerenes and a sugar-functionalized tribenzotriquinacene assembling to microspheres

• Si-Yuan Liu,
• Xin-Rui Wang,
• Man-Ping Li,
• Wen-Rong Xu and
• Dietmar Kuck

Beilstein J. Org. Chem. 2020, 16, 2551–2561, doi:10.3762/bjoc.16.207

• shallow cavity of the parent TBTQ hydrocarbons, thus allowing for the inclusion of large guest molecules, such as the fullerenes. Several TBTQ derivatives with extended cavities have been developed by us and other groups. Volkmer et al. designed a series of novel TBTQ-based receptors, 1–3, and studied

How and why plants and human N-glycans are different: Insight from molecular dynamics into the “glycoblocks” architecture of complex carbohydrates

• Carl A. Fogarty,
• Aoife M. Harbison,
• Amy R. Dugdale and
• Elisa Fadda

Beilstein J. Org. Chem. 2020, 16, 2046–2056, doi:10.3762/bjoc.16.171

• , implicated in protein folding and structural stability, and mediating interactions with receptors and with the environment. All N-glycans share a common core from which linear or branched arms stem from, with functionalization specific to different species and to the cells’ health and disease state. This

• of the N-glycan and its structural dynamics, therefore its selective recognition by lectin receptors and antibodies. The atomistic-level of detail information that the MD simulations provide us with, highlights that the effects of different functionalizations, in terms of monosaccharide types and

Design, synthesis and application of carbazole macrocycles in anion sensors

• Alo Rüütel,
• Ville Yrjänä,
• Sandip A. Kadam,
• Indrek Saar,
• Mihkel Ilisson,
• Astrid Darnell,
• Kristjan Haav,
• Tõiv Haljasorg,
• Lauri Toom,
• Johan Bobacka and
• Ivo Leito

Beilstein J. Org. Chem. 2020, 16, 1901–1914, doi:10.3762/bjoc.16.157

• sensor development, the results obtained in this work emphasize the importance of evaluating the binding behavior of receptors in real sensor membranes. Keywords: anion sensors; carboxylates; ionophores; macrocycles; sensor prototype; Introduction In 2013, Otto S. Wolfbeis asked the supramolecular

• recognition elements of chemical sensors. However, the research typically ended with demonstration of the ability of analyte binding. Rarely have the receptors found their way into functioning chemical sensor prototypes. The reason for this is that the step from a well-binding receptor to a sensor prototype

• moiety fulfils several key design requirements. At least four hydrogen bonding sites (N–H groups) are available and positioned in a favourable geometry for carboxylates. Additional hydrogen-bond-donor (HBD) groups can be added with substituents. The solubility of such receptors can be tuned using

A dynamic combinatorial library for biomimetic recognition of dipeptides in water

• Florian Klepel and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2020, 16, 1588–1595, doi:10.3762/bjoc.16.131

• receptors emerging form a dynamic combinatorial library of peptide building blocks. In this study we aimed to broaden this scope towards recognition of small peptides. Employing CXC peptide building blocks, we found that cyclic dimers of oxidized CFC bind to the aromatic peptides FF and YY (K ≈ 229–702 M−1

• motifs were developed and if arranged correctly can be used to synthesize artificial receptors with high affinity [2][3]. Schmuck et al. have been hugely successful in designing artificial peptide receptors [4][5]. For example, they combined a carboxylate binding site with an aromatic bowl-shaped cavity

• . A more general approach for the development of artificial receptors can be the use of a dynamic combinatorial library (DCL). In a DCL a large variety of molecules is generated by a dynamic exchange of building blocks. The dynamic nature of those exchange reactions is essential since it allows the

Activated carbon as catalyst support: precursors, preparation, modification and characterization

• Melanie Iwanow,
• Tobias Gärtner,
• Volker Sieber and
• Burkhard König

Beilstein J. Org. Chem. 2020, 16, 1188–1202, doi:10.3762/bjoc.16.104

• significant time reduction and therefore energy savings [103]. The major problem of microwave heating is that the carbon sources are poor receptors for the irradiation, thus activation agents are necessary as heat carriers and for promotion of porosity [104]. Wang et al. prepared activated carbons with high

Diversity-oriented synthesis of 17-spirosteroids

• Benjamin Laroche,
• Thomas Bouvarel,
• Martin Louis-Sylvestre and
• Bastien Nay

Beilstein J. Org. Chem. 2020, 16, 880–887, doi:10.3762/bjoc.16.79

• has been previously used to generate medicinally relevant diversity in other compound series [49][55][56][57][58]. However, it has surprisingly never been applied to 17-ethynyl-17-hydroxysteroids. Most steroids bind cytosolic receptors that are then taken up into the nucleus to modulate gene

• transcription, or directly bind nuclear receptors [59][60][61]. In principle, steroids could thus be used as cargo molecules to deliver new chemical entities inside the nucleus, highlighting the potential of hybrid steroid molecules [62]. For example, De Riccardis designed steroid scaffolds directly fused to a

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• analysis is a well-established technique that is utilized to evaluate interactions in important biological receptors such as that of HDACs [28][29][30]. Previously, we implored docking to predict the interactions between the active sites of HDAC2 and HDAC8 molecular frameworks with similar structures to

Two antibacterial and PPARα/γ-agonistic unsaturated keto fatty acids from a coral-associated actinomycete of the genus Micrococcus

• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku,
• Nobuyasu Matsuura,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 297–304, doi:10.3762/bjoc.16.29

• preference that 1 is more effective to the former strain while 2 is so to the latter. In addition, compounds 1 and 2 displayed agonistic activity against peroxisome proliferator-activated receptors (PPARs) with an isoform specificity towards PPARα and PPARγ. Keywords: antibacterial; coral; keto fatty acid

• cytotoxicity against murine leukemia P388 cells at 100 µM. Additionally, compounds 1 and 2 were evaluated for agonist activity to peroxisome proliferator-activated receptors (PPARs) because similar oxo fatty acids are known to act as PPAR agonists [42]. PPARs are ligand-activated transcription factors playing

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

• -step synthetic approach allowed the installation of a trimethylammonium (TA) head onto the 4FAB scaffold, by means of an alkyl spacer, to afford a free diffusible 4FABTA probe. TAs are known to agonize nicotinic receptors, so 4FABTA was tested on mouse brain slices and enabled reversible receptor

• . Keywords: acetylcholine receptors; bidirectional; photoswitchable drug; tetrafluoroazobenzene; visible light; Introduction Starting in 1937, azobenzenes (ABs) have attracted much attention because they undergo a photoreversible chemical transformation of the thermodynamically favored trans configuration

• regular AB-based photoswitch called "MAHoCh" [16]. The MAHoCh probe was originally designed [16] to activate nicotinic acetylcholine receptors in vivo. However, it was found that the trimethylammonium (TA) head group blocked acetylcholine binding when the photoprobe was cross-linked to the channel near

An improved, scalable synthesis of Notum inhibitor LP-922056 using 1-chloro-1,2-benziodoxol-3-one as a superior electrophilic chlorinating agent

• Nicky J. Willis,
• Elliott D. Bayle,
• George Papageorgiou,
• David Steadman,
• Benjamin N. Atkinson,
• William Mahy and
• Paul V. Fish

Beilstein J. Org. Chem. 2019, 15, 2790–2797, doi:10.3762/bjoc.15.271

• Wnt proteins is required for efficient binding to Frizzled receptors and the subsequent signal transduction. The carboxylesterase Notum has been shown to act as a key negative regulator of the Wnt signalling pathway by specifically mediating the depalmitoleoylation of Wnt proteins [3][4]. LP-922056 (1

Arylisoquinoline-derived organoboron dyes with a triaryl skeleton show dual fluorescence

• Vânia F. Pais,
• Tristan Neumann,
• Ignacio Vayá,
• M. Consuelo Jiménez,
• Abel Ros and
• Uwe Pischel

Beilstein J. Org. Chem. 2019, 15, 2612–2622, doi:10.3762/bjoc.15.254

• receptors for fluoride anions. Experimental General methods and materials 1H NMR spectra were recorded at 400 MHz or 500 MHz and 13C NMR spectra were recorded at 100 MHz or 125 MHz. Chloroform-d (CDCl3), acetone-d6 ((CD3)2CO) and benzene-d6 (C6D6) were used as solvents and the solvent peak was employed as

Synthetic terpenoids in the world of fragrances: Iso E Super^® is the showcase

• Alexey Stepanyuk and
• Andreas Kirschning

Beilstein J. Org. Chem. 2019, 15, 2590–2602, doi:10.3762/bjoc.15.252

• -protein receptors consisting of seven intermembrane domains [28]. The quaternary structure including the membrane set up the active site. Approximately 370 different G-type proteins are known, that are linked with the odour perception. Because molecules can bind to an array of olfactory receptors

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

• full agonism. The compound class disclosed here can aid in new photopharmacology studies of CXCR3 signaling. Keywords: azo compounds; chemokine receptor; efficacy photoswitching; G protein-coupled receptors; photopharmacology; Introduction Photopharmacology is an emerging discipline at the interface

• 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