Targeting active site residues and structural anchoring positions in terpene synthases

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 2441–2449, doi:10.3762/bjoc.17.161

• incorporated by its nucleophilic attack at a cationic intermediate, leading to terpene alcohols [5][6] or sometimes ethers [7][8]. Substrate ionisation by TPSs is achieved through binding of the diphosphate portion to a trinuclear Mg2+ cluster in the active site that is itself bound to two highly conserved

• of the pyrophosphate sensor) that form a salt bridge between helices F and G [12][13][14], and a conserved Asn (8 or 9 residues downstream of the NSE triad) that hydrogen bridges to the Mg2+ binding Glu of the NSE triad [15]. In between these structural anchors the amino acid sequences of terpene

• large active site cavity SmTS1 exhibits a few notable features within its amino acid sequence. The aspartate-rich motif, that is usually composed of DDXX(X)D and is responsible for binding of two Mg2+ cations (Figure 1) [11][21], is modified to N86DLTV in SmTS1. Similarly, the NSE triad for binding of

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• captivated synthetic chemists and biologists alike since the 1960s due to their efficient DNA binding, antitumour and antiparasitic activities [1]. Such compounds include the DNA and RNA-fluorescent marker ethidium bromide (1), the cell viability probe propidium iodide (2) and the naturally occurring

Post-functionalization of drug-loaded nanoparticles prepared by polymerization-induced self-assembly (PISA) with mitochondria targeting ligands

• Janina-Miriam Noy,
• Fan Chen and
• Martina Stenzel

Beilstein J. Org. Chem. 2021, 17, 2302–2314, doi:10.3762/bjoc.17.148

• to mitochondrial protein, but also chelates other cysteine-containing species. Several hundred good binding sites for trivalent arsenicals in each organ have been proposed [6][7], and more than 50 arsenic-binding proteins could be identified and analysed by Zhang et al. [8] and Yan et al. [9] using p

• mitochondria binding ligand does not induce any damaging effects to these cell lines. Many studies have reported that attaching targeting ligands on nanoparticle or liposome surfaces play a key role in overcoming biological barriers and reducing targeting effects. Active targeting or retention can increase

• binding of biorecognition molecules on a PEG nanoparticle to its target only works when the PEG chain length is less than the polymer chain to which the ligand is attached. Otherwise, the long PEG chain will intercept ligand binding [50]. It is also reasonable to think that TPP is barely visible on the

Synthesis of O⁶-alkylated preQ₁ derivatives

• Laurin Flemmich,
• Sarah Moreno and
• Ronald Micura

Beilstein J. Org. Chem. 2021, 17, 2295–2301, doi:10.3762/bjoc.17.147

• class-I riboswitch [1]. This riboswitch acts as a ribozyme by using 7-aminomethyl-O6-methyl-7-deazaguanine (m6preQ1) as methyl group donor; it catalyzes self-methylation of a specific cytidine in the aptamer binding pocket, yielding N3-methyl cytidine (m3C) under release of 7-aminomethyl-7-deazaguanine

• thereby regulates genes that are required for queuosine biosynthesis [8][9][10][11][12][13][14][15][16]. The molecular mechanism behind is called riboswitching. For most riboswitches, ligand binding induces a structural change in the untranslated leader sequence of mRNA by formation (or disruption) of a

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• development of the research area of asymmetric anion-binding organocatalysis. Key early elucidation studies with chloride as counter-anion confirmed this type of alternative activation, which was then exploited in several processes and contributed to the advance and consolidation of anion-binding catalysis as

• the cationic reactive species. Keywords: anion binding; asymmetric catalysis; halide anions; hydrogen donors; noncovalent interactions; Introduction Halogens and the respective anionic halides occupy an essential role in natural and chemical processes [1][2][3][4]. While in chemical syntheses

• challenging to design small molecule catalysts that resemble anion-binding properties of enzymes. Hence, a major challenge of small organic receptors to mimic nature’s capability of binding to the targeted anions resides in the supramolecular properties of enzymes and co-factors to form exact matching binding

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• , with IC50 values between 1.0 and 7.3 μM, and were subjected to molecular docking studies. The results suggest that such compounds can interact at the same binding site as imatinib, probably sharing a competitive inhibition mechanism. One compound showed the greatest interaction affinity for BCR-Abl-1

• TKIs that are even more potent than IMT, such as nilotinib [6][7]. These drugs act as inhibitors at the ATP binding site in the inactive form of BCR-Abl-1, preventing the binding of the protein to ATP in a competitive manner and resulting in the interruption of the substrate phosphorylation process and

• interact with BCR-Abl-1 at the same binding site as IMT but show differences in the binding modes and with higher values of interaction energy. Compound 2c presented a MolDock value of −152.993 a.u. For compound 2d, the value was −152.127 a.u., and for compound 2g, it was −167.520 a.u. (Table 2

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

Enantioenriched α-substituted glutamates/pyroglutamates via enantioselective cyclopropenimine-catalyzed Michael addition of amino ester imines

• Zara M. Seibel,
• Jeffrey S. Bandar and
• Tristan H. Lambert

Beilstein J. Org. Chem. 2021, 17, 2077–2084, doi:10.3762/bjoc.17.134

• reported [45], for which a detailed transition state model was developed. In that study, it was determined that the reaction proceeds via several competing low-energy transition states involving both O–H and N–H enolate binding modes, E and Z enolate isomers, and a range of H-bonding and other noncovalent

• enolate geometry and N–H vs O–H binding). From this transition state, addition of the enolate to the acrylate followed by rapid proton transfer would lead to the glutamate derivative 10 (path a, red dashed line). A competing pathway involving bond formation between the acrylate α-carbon and the imine

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• substitution. A collection of linear β(1–4)-ᴅ-xylan chains and with α(1–3)-ʟ-arabinofuranosyl branches was quickly assembled to identify the binding epitopes of monoclonal antibodies. These oligomers, together with other well-defined analogues obtained by chemoenzymatic synthesis, were converted to the

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• the desired transformation by using only one catalyst [70]. In this sense, an efficient asymmetric organocatalytic reaction was reported by Zhang et al. for the synthesis of 2,8-dioxabicyclo[3.3.1]nonanes [71]. A combination of catalysts 7 and 110, involving iminium and anion-binding catalysis

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• Mathias B. Danielsen Jesper Wengel Biomolecular Nanoscale Engineering Center, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark 10.3762/bjoc.17.125 Abstract Antisense oligonucleotides (ASOs) have the ability of binding to

• nuclease resistance, increased binding to the nucleic acid target and improved cell uptake for oligonucleotides (ONs) and ASOs. The modifications highlighted in this review are some of the most prevalent cationic amine groups which have been attached as single modifications onto ONs/ASOs. The review has

• target generally are of the gapmer-design class (Figure 1), where a central segment of at least five DNA nucleotides termed the 'gap' is flanked by modified nucleotides that promote target binding and protection against exonucleolytic degradation [2]. Another class are the steric block ASOs that bind to

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• protein–ligand binding properties as well as biological activities of small molecules, potentially leading to dramatic increases in potency, and thus has been widely explored in drug discovery [54][55][56]. Late-stage C–H methylation has recently been investigated using iron and cobalt catalysts as

A systems-based framework to computationally describe putative transcription factors and signaling pathways regulating glycan biosynthesis

• Theodore Groth,
• Rudiyanto Gunawan and
• Sriram Neelamegham

Beilstein J. Org. Chem. 2021, 17, 1712–1724, doi:10.3762/bjoc.17.119

• termed glycogenes [1][2]. These glycogenes include the glycosyltransferases, glycosidases, sulfotransferases, transporters, etc. The expression of these glycogenes is in turn driven by the action of a class of proteins called transcription factors (TFs). These TFs regulate gene expression by binding

• proximal to the promoter regions of genes, facilitating the binding of RNA polymerases. They may homotropically or heterotropically associate with additional TFs in order to directly or indirectly control messenger RNA (mRNA) expression. Among the TFs, some “pioneer factors” can pervasively regulate gene

• their tissue-specific expression, DNA binding domains, and nucleosome interaction sequences [3]. Additional factors regulating transcriptional activity include: i) cofactors and small molecules that enable TF-DNA recognition and RNA polymerase recruitment [3]; ii) chromatin modifications, such as

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• and diagnostics, and attempts to develop new PNA therapeutics. The discussion starts with a brief review of PNA’s binding modes and structural features, followed by the most impactful chemical modifications, PNA enabled assays and diagnostics, and discussion of the current state of development of PNA

• therapeutics. While many modifications have improved on PNA’s binding affinity and specificity, solubility and other biophysical properties, the original PNA is still most frequently used in diagnostic and other in vitro applications. Development of therapeutics and other in vivo applications of PNA has

• electrostatic repulsion. The maintenance and function of long double-stranded DNA (dsDNA) is achieved through complex mechanisms involving histones and other proteins. Large non-coding RNAs (e.g., ribosomes) manage electrostatic repulsion using positively charged RNA-binding proteins and cations (e.g

Recent advances in the application of isoindigo derivatives in materials chemistry

• Andrei V. Bogdanov and
• Vladimir F. Mironov

Beilstein J. Org. Chem. 2021, 17, 1533–1564, doi:10.3762/bjoc.17.111

• the introduction of aromatic substituents of variable nature into the oligomer structure. By the example of pyrene derivatives 7 and 8, the dependence of the binding type of the aromatic fragment to the isoindigo core was revealed. The synthetic procedure for the preparation of these monoisoindigoid

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• therapeutic potential. In addition, trans-4-phenyl-N,N-dimethyl-2-aminotetralin (trans-H2-PAT, 4, Figure 1) [6] has been determined to modulate tyrosine hydroxylase activity and dopamine synthesis in rodent forebrain and is also a ligand binding to histamine H1 receptors, and thus is a potentially useful

Iodine-catalyzed electrophilic substitution of indoles: Synthesis of (un)symmetrical diindolylmethanes with a quaternary carbon center

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati,
• Andhika B. Mahardhika,
• Lukas L. Wendt and
• Christa E. Müller

Beilstein J. Org. Chem. 2021, 17, 1464–1475, doi:10.3762/bjoc.17.102

• , and scalability to obtain gram amounts for biological studies. Selected compounds were found to display affinity for cannabinoid receptors, which are promising drug targets for the treatment of inflammatory and neurodegenerative diseases. Keywords: alkylation of indole; anti-inflammatory; binding

• via an iodine-catalyzed coupling reaction of trifluoromethyl(indolyl)phenylmethanol with indole derivatives. This method has also been extended to the synthesis of pentafluoro-ethylated and heptafluoro-propylated DIMs in excellent yields. Selected compounds were evaluated in radioligand binding

• previously reported to bind to the cannabinoid receptors, CB1 (Ki 4.3 µM) and CB2 (Ki 1.1 µM) [41]. Both receptors are considered important therapeutic targets, e.g. for neurodegenerative and inflammatory diseases. Selected final products (3a, 3b, 3e, 3g, 3h, 3n, 3ad) were tested for their binding affinities

Antiviral therapy in shrimp through plant virus VLP containing VP28 dsRNA against WSSV

• Santiago Ramos-Carreño,
• Ivone Giffard-Mena,
• Jose N. Zamudio-Ocadiz,
• Alfredo Nuñez-Rivera,
• Ricardo Valencia-Yañez,
• Jaime Ruiz-Garcia,
• Maria Teresa Viana and
• Ruben D. Cadena-Nava

Beilstein J. Org. Chem. 2021, 17, 1360–1373, doi:10.3762/bjoc.17.95

• entry, binding and assembly of the virion. Previous studies have shown that silencing these structural proteins in WSSV challenge assays, increases shrimp survival [10][11][17][18][19][20][21]. The VP28 glycoprotein plays an important role in systemic infection by interacting with cell membrane proteins

• dsRNAvp28 at 3.0, 2.0, 1.0, and 0.5 µg, WSSV-Negative control received a 3.0 µg dose. The survival was evaluated up to 504 hpi (21 days). (D) Oral antiviral treatment with VLP-dsRNAvp28 (6 µg per shrimp) in the pellet with fish oil (industrial grade) as a binding agent. Different letters (a–d) in each

Photoinduced post-modification of graphitic carbon nitride-embedded hydrogels: synthesis of 'hydrophobic hydrogels' and pore substructuring

• Cansu Esen and
• Baris Kumru

Beilstein J. Org. Chem. 2021, 17, 1323–1334, doi:10.3762/bjoc.17.92

• synthesis [32][33][34][35]. Integration of g-CN into hydrogels has been popularized in the last four years, where g-CN nanosheets can be implemented into hydrogels through embedding [36] or covalent binding [37][38] for the target application such as reinforced hydrogels [39] and hydrogels for photoredox

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Structural effects of meso-halogenation on porphyrins

• Keith J. Flanagan,
• Maximilian Paradiz Dominguez,
• Zoi Melissari,
• Hans-Georg Eckhardt,
• René M. Williams,
• Dáire Gibbons,
• Caroline Prior,
• Gemma M. Locke,
• Alina Meindl,
• Aoife A. Ryan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2021, 17, 1149–1170, doi:10.3762/bjoc.17.88

• some cases can be undesirable. Recent studies from our group have been carried out on the use of halogens as a binding motif in cubanes [15], bicyclo[1.1.1]pentane [16], and nonplanar porphyrins [17]. Another reason to investigate the effect of meso-halogenation of porphyrins is due to the potential of

• [18], the conformation of the porphyrin core can play a key role in the binding of small molecules or on its efficiency as an organocatalyst as demonstrated by Roucan et al. [19]. With the continuing interest in nonplanar porphyrins [20] and their relevance for the in vivo functioning of porphyrin

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• alkaloids that were isolated in the mid-1990s from the Caribbean sponge bataella sp. From a biological point of view, the batzelladines have received attention due to their reported activity as inhibitors of HIV gp120-human CD4 binding. Chiral N-tert-butanesulfinyl aldimine (SS)-58 was used as a precursor

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• . Keywords: amino sugars; deoxyfluorination; fluorinated carbohydrates; hexosamine hemiacetals; thioglycosides; Introduction Fluorinated carbohydrates are versatile carbohydrate mimetics used to probe or manipulate the recognition of carbohydrates by carbohydrate-binding proteins or carbohydrate-processing

• enzymes [1][2][3][4][5][6][7]. The introduction of additional fluorine atoms into a monofluorinated carbohydrate is an attractive way of modulating the binding affinity and pharmacokinetic properties of fluorinated glycomimetics. Hydrophobic segments incorporating multiple C–F bonds could (1) reduce the

• desolvation penalty associated with binding of hydrophilic natural carbohydrates [8], and (2) create additional contacts with the binding cavity via electrostatic and dipolar interactions with C–F bonds [9][10], new intermolecular hydrogen bonds [11], or rearrangement of hydrogen bond-mediating water

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82