Cell-free protein synthesis with technical additives – expanding the parameter space of in vitro gene expression

• Tabea Bartsch,
• Stephan Lütz and
• Katrin Rosenthal

Beilstein J. Org. Chem. 2024, 20, 2242–2253, doi:10.3762/bjoc.20.192

• , batch-to-batch reproducibility, and reliable kinetic modelling of the system [10][11]. Furthermore, the transferability of CFPS screening results to the cells is limited but important, as in vivo production is often required for preparative scale applications [11][12]. To date, the description of CFPS

• concentration in the CFPS system is lower than that in the cells. It was therefore increased by the addition of DES, which have already been used for biological applications [52] and are considered as promising environmentally friendly alternative solvents [53]. The addition of choline chloride appears to have

• Equation 1 [64], as only minor influences are assumed at the concentrations used in this work: The concentration of macromolecules was calculated based on the cytosolic composition and the average OD600 at the harvest of the culture for the cell-free extract. With the derived number of cells, the cellular

Metal-free double azide addition to strained alkynes of an octadehydrodibenzo[12]annulene derivative with electron-withdrawing substituents

• Naoki Takeda,
• Shuichi Akasaka,
• Susumu Kawauchi and
• Tsuyoshi Michinobu

Beilstein J. Org. Chem. 2024, 20, 2234–2241, doi:10.3762/bjoc.20.191

• high efficiency under physiologically active conditions and the absence of any toxic metal ions. SpAAC is biorthogonal, which allows for the specific labeling and imaging of biomolecules even in living cells and organisms. Recently, a more rapid click reaction was desired and the strain-promoted

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• solubility in the standard tests, performed in aqueous media) nor phytotoxic activity [73]. A general but not an acute toxicity of AOH has already been mentioned in late 1970ies, e.g., an activity against Bacillus mycoides at 60 μg/disc and a toxicity to HeLa cells with an ID50 value of 6 μg/mL [74]. It

• turned out that induced cytotoxicity [75] is mediated by activation of the mitochondrial pathway of apoptosis in human colon carcinoma cells [76][77] and that cytotoxicity on HCT116 cells is increased, when AOH is combined with 9-O-methylalternariol (2, AME) [78]. AOH further showed to have a detrimental

• V79 cells and in mouse lymphoma cells even at non-toxic or moderately cytotoxic concentrations [84]. AOH was further shown to cause strand-breaking in mammalian cell lines V79, HepG2, and HT-29 [85][86][87]. It was a significant finding by Marko et al. that AOH acts as a topoisomerase poison

Novel truxene-based dipyrromethanes (DPMs): synthesis, spectroscopic characterization and photophysical properties

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2024, 20, 2163–2170, doi:10.3762/bjoc.20.186

• ][12][13]. The most promising applications of truxene-based systems have been found in organic photovoltaics (OPVs), dye‐sensitized solar cells (DSSCs), fluorescent probes, organic thin‐film transistors (OTFTs), lasers, organic light emitting diodes (OLEDs), liquid crystals, non-linear optical (NLO

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

Cage-like microstructures via sequential Ugi reactions in aqueous emulsions

• Rita S. Alqubelat,
• Yaroslava A. Menzorova and
• Maxim A. Mironov

Beilstein J. Org. Chem. 2024, 20, 2078–2083, doi:10.3762/bjoc.20.179

• substances [7]. A particularly interesting area is the use of colloidosomes to model processes in living cells and produce artificial protocells [8][9]. The enlargement of pores on the surface of colloidosomes leads to structures that resemble microscopic cages [10]. Obtaining such cage-like structures is

Allostreptopyrroles A–E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384

• Marwa Elsbaey,
• Naoya Oku,
• Mohamed S. A. Abdel-Mottaleb and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2024, 20, 1981–1987, doi:10.3762/bjoc.20.174

• by formyl and carboxyl functionalities. Compounds 1, 4, and 5 showed cytotoxicity against Kasumi-1 human acute myeloblastic leukemia cells with IC50 values of 103, 105, and 105 μM, respectively, which are less active than the anticancer agent cisplatin, with an IC50 value of 70 μM. Keywords

• cytotoxicity against Kasumi-1 human acute myeloblastic leukemia cells with IC50 values of 103, 105, and 105 while 2 and 3 were less active with IC50 values of 200 and 333 μM, respectively. Under the same experimental conditions, cisplatin, a positive control, inhibited the cell growth with an IC50 value of 70

A new platform for the synthesis of diketopyrrolopyrrole derivatives via nucleophilic aromatic substitution reactions

• Vitor A. S. Almodovar and
• Augusto C. Tomé

Beilstein J. Org. Chem. 2024, 20, 1933–1939, doi:10.3762/bjoc.20.169

• used in a wide range of applications, namely as organic semiconductors [8], acceptors for organic solar cells [9][10], as fluorescent probes [11][12][13], or as photosensitizers for photodynamic therapy and antimicrobial photodynamic therapy [14][15][16][17]. DPP derivatives with improved performance

Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• activity and thus block cancer formation [2]. Alangiumkaloids A, an isoquinolinone alkaloid isolated from Alangium salviiforlium, was reported to exhibit cytotoxic activity against cancer cells [3]. In 2018, duvelisib, a dual inhibitor of phosphoinositide-3 kinases, was firstly approved by the FDA for the

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• , commercial compound 1 (Scheme 2) represents a rescaffolding exercise to pyridine retaining low inhibitory activity although it was found toxic in in vitro assays on a human T-cell line and PBMCs (periferal blood mononuclear cells). The derivatives (R)-2 and (S)-2 were elaborated by Berger et al. [7] in the

• acid (46). The major source of histamine are mast cells, although it is additionally biosynthesized in basophils, other immune cells, and tissues like intestinal mucosa, skin, or the heart [45][48]. Histamine plays many pivotal roles in the onset of allergies via Th2 cytokine secretion and inhibition

• of Th1 cytokine, leukotriene and chemokines release, or IL-6 induction. Histamine targets histamine receptors H1–4, triggering pro-inflammatory or anti-inflammatory events depending on the receptor type and cells involved [45][49]. Histamine also plays a critical role in both vertebrates and

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity

• Moisés Alejandro Alejo Hernandez,
• Katia Pamela Villavicencio Sánchez,
• Rosendo Sánchez Morales,
• Karla Georgina Hernández-Magro Gil,
• David Silverio Moreno-Gutiérrez,
• Eddie Guillermo Sanchez-Rueda,
• Yanet Teresa-Cruz,
• Brian Choi,
• Armando Hernández Garcia,
• Alba Romero-Rodríguez,
• Oscar Juárez,
• Siseth Martínez-Caballero,
• Mario Figueroa and
• Corina-Diana Ceapă

Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159

• CloM1 and CloM2 with the CylM enzyme (PDB code: 5DZT). For the structural alignment of CloPt1 and CloPt2, the characterized protein PCAT1 (PDB code: 3QF4) was analyzed. Gene expression in E. coli and purification of CloA1 and CloA2 precursor peptides and C39 peptidase domain E. coli NiCO21 (DE3) cells

• 0.8. Cultures were incubated for 14 h, at 200 rpm, at 18 °C. Subsequently, cells were centrifuged at 10,000 rpm for 30 min at 4 °C. The resulting cell pellets were resuspended in 20 mL of LanA starting buffer (20 mM Tris pH 7.5, 500 mM KCl, 10% glycerol) and lysed by sonication (4.0 seconds on, 10

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• 30 were obtained in moderate yields (ranging from 29% to 50%, Scheme 9) and were tested as anti-inflammatory drugs in RAW 264.7 cells and as inhibitors of rat ear edema. Unfortunately, the tested compounds exhibited weak activity in all assays. Khripach et al. reported a three-step sequence for the

• . Chromatographic purification was not required post-reaction. Some spiro products exhibited high binding affinity towards DNA, while others showed good cytotoxicity against different cancer cells (A545, MCF-7, HeLa, HL-60, SW480, HepG2, HT-29, and A549) with IC50 values within the micromolar range (2.18–18.54 µM

• synthesized compounds were evaluated for their DNA binding properties and screened for cytotoxicity against leukemia cancer cells (Jurkat), demonstrating IC50 values in the micromolar range (14.2 to 36.5 µM). Importantly, these derivatives exhibited minimal toxicity toward normal cells (PBMCs). Furthermore

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• synthesized 44 and 47 with cultured M. alba cells. The formation of both diene 48 and DA adduct 3 were observed, indicating that M. alba cells harbor the key enzymes MaMO and MaDA. Based on these results, synthetic analogs of intermediate 44 were designed and exposed to the M. alba cells to explore the

• subsequently overexpressed in insect cells and purified as soluble proteins, culminating in the elucidation of the X-ray crystallographic structure of MaDA (Scheme 5B, PDB: 6JQH). With these key enzymes in hand, Lei and co-workers conducted a chemo-enzymatic total synthesis of 3 and related natural products

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• proteusin family of RiPPs. They are produced by the tunicate symbiont Candidatus Entotheonella factor and exhibit membrane activity against Gram-positive bacteria and are highly cytotoxic. Cytotoxicity was tested with murine leukaemia cells; polytheonamide A, B, and C showed IC50 values between 68 and 78 pg

• member of the channel-forming, cytotoxic proteusins. It is biosynthesised by Microvirgula aerodenitrificans. Like polytheonamide B, aeronamide A shows cytotoxic activity against HeLa cells, with an IC50 of 1.48 nM. AerE, the PoyE homologue, installs five methylations on the amides of Asn25, Asn31, Asn37

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• agarase was also reported from the same bacterium [27]. The recombinant enzyme (rAgaO) was expressed in B. subtilis cells to demonstrate that this enzyme was an endo-type β-agarase and degraded agarose to neoagarohexaose as the main product [27]. The enzyme rAgaO represents the first and only report on

• Gram-positive bacteria Kocuria rhizophila and S. aureus, Gram-negative bacterium Tenacibaculum maritimum, and a panel of fungi. These molecules also demonstrated moderate cytotoxicity against P388 murine leukemia cells. The bisindole alkaloid violacein (24, Figure 8) was isolated and characterized from

New triazinephosphonate dopants for Nafion proton exchange membranes (PEM)

• Fátima C. Teixeira,
• António P. S. Teixeira and
• C. M. Rangel

Beilstein J. Org. Chem. 2024, 20, 1623–1634, doi:10.3762/bjoc.20.145

• . Romão Ramalho, 59, 7000-671 Évora, Portugal 10.3762/bjoc.20.145 Abstract A new paradigm for energy is underway demanding decarbonized energy systems. Some of them rely on emerging electrochemical devices, crucial in hydrogen technologies, including fuel cells, CO2 and water electrolysers, whose

• N115, in the same experimental conditions. The Nafion-doped membrane with compound TP2 with a 1.0 wt % loading showed the highest proton conductivity with 84 mS·cm−1. Keywords: electrolyser; fuel cells; Nafion-modified membranes; phosphonates; proton exchange membranes; triazine; Introduction

• exchange membrane devices [5][6], such as proton exchange membrane fuel cells (PEMFCs) [3][7][8][9], due to their high-power density and high power-to-weight ratio, and CO2 electrolysers, which can reduce the polluting gas CO2 and produce syngas from the co-electrolysis of CO2 and water [10][11], or water

Supramolecular assemblies of amphiphilic donor–acceptor Stenhouse adducts as macroscopic soft scaffolds

• Ka-Lung Hung,
• Leong-Hung Cheung,
• Yikun Ren,
• Ming-Hin Chau,
• Yan-Yi Lam,
• Takashi Kajitani and
• Franco King-Chi Leung

Beilstein J. Org. Chem. 2024, 20, 1590–1603, doi:10.3762/bjoc.20.142

• functionalized with photoresponsive and photoabsorbing functional motifs, serving as the counterpart of natural photosystems. This allowed to construct smart materials that harvest light energy, e.g., solar cells, photosensitizers, and photochromic materials [1][2][3][4]. Supramolecular assemblies are commonly

• prepared by ejecting 5.0 wt % DAn solutions onto a bioinert glass-bottomed Petri dish by the shear-flow method, rinsing with PBS, and incubating with human-bone-marrow-derived mesenchymal stem cells (hBM-MSCs) at 37 °C and 5% CO2 for 3 days. hBM-MSCs have demonstrated importance in controlled

• differentiations and clinical translations. The DA11 scaffold remained intact after incubation at 37 °C, while the hBM-MSCs cells grew and attached onto the scaffold surface (Figure 6a and Figure 6b). However, the structural properties of the macroscopic soft DA11 scaffold could not be transferred to the attached

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• ] or to mannosyl azobenzene-modified human cells [21] through photoswitching the orientation of the attached mannoside [22]. Photoswitchable glycooligomers [23] or glycodendrimers [24] have been investigated for the inhibition of PA lectin PA-IL or LecA and LecB. A variation of the IC50 value by a

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• seven analogs for cytotoxicity against human colon carcinoma HCT-116 cells. Unfortunately, none of the compounds up to 10 μM showed any activity when tested in MTT-based cell viability assays. Conclusion Eunicellane diterpenoids have been known for over 50 years, but it was not until recently that their

Sustainable tandem acylation/Diels–Alder reaction toward versatile tricyclic epoxyisoindole-7-carboxylic acids in renewable green solvents

• Ayhan Yıldırım

Beilstein J. Org. Chem. 2024, 20, 1308–1319, doi:10.3762/bjoc.20.114

• oligopeptidase inhibitory activity in human cells [117]. The solvent mixture used to precipitate the product was removed from the filtrate using a rotary evaporator and it was found that the used bio-based solvents could be recovered in a near quantitative amount for reuse. The recovered SSO solvent was reused

Synthesis of indano[60]fullerene thioketone and its application in organic solar cells

• Yong-Chang Zhai,
• Shimon Oiwa,
• Shinobu Aoyagi,
• Shohei Ohno,
• Tsubasa Mikie,
• Jun-Zhuo Wang,
• Hirofumi Amada,
• Koki Yamanaka,
• Kazuhira Miwa,
• Naoyuki Imai,
• Takeshi Igarashi,
• Itaru Osaka and
• Yutaka Matsuo

Beilstein J. Org. Chem. 2024, 20, 1270–1277, doi:10.3762/bjoc.20.109

• -withdrawing substituents. Computational studies with density functional theory revealed the unique vibrations of the thioketone group in FIDS. The molecular structure of FIDS was confirmed by single-crystal X-ray analysis. Bulk heterojunction organic solar cells using three evaporable fullerene derivatives

• (FIDO, FIDS, C60) as electron-acceptors were compared, and the open-circuit voltage with FIDS was 0.16 V higher than that with C60. Keywords: C60; evaporable fullerene derivatives; organic photovoltaics; organic solar cells; thioketone; Introduction Fullerene is a carbon allotrope that has attracted

• improving their thermal stability, and more specifically, of designing evaporable fullerene derivatives [16][17][18]. Recently, we reported on perovskite solar cells fabricated with indano[60]fullerene ketone (FIDO), which was synthesized through fullerene cation chemistry. These cells demonstrated long

Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis

• Jinmin Gao,
• Liyuan Li,
• Shijie Shen,
• Guomin Ai,
• Bin Wang,
• Fang Guo,
• Tongjian Yang,
• Hui Han,
• Zhengren Xu,
• Guohui Pan and
• Keqiang Fan

Beilstein J. Org. Chem. 2024, 20, 1198–1206, doi:10.3762/bjoc.20.102

• . Both plasmids were confirmed by sequencing and transformed into E. coli BL21(DE3). Protein overproduction was induced with 0.1 mM isopropyl β-ᴅ-thiogalactopyranoside at 16 °C for 15 h. Cells were collected by centrifugation (8,000g, 15 min) at 4 °C. The pellets were resuspended in ice-cold 50 mM 3-(N

• -morpholino)propanesulfonic acid (MOPS) buffer (pH 7.5), and the cells were disrupted by ultrasonication to obtain the cell extract. Cell debris was removed by centrifugation (14,000g, 15 min). The proteins were purified by Ni-NTA agarose chromatography, desalted, and concentrated by centrifugation (8,000g

Two-fold addition reaction of silylene to C₆₀: structural and electronic properties of a bis-adduct

• Masahiro Kako,
• Masato Kai,
• Masanori Yasui,
• Michio Yamada,
• Yutaka Maeda and
• Takeshi Akasaka

Beilstein J. Org. Chem. 2024, 20, 1179–1188, doi:10.3762/bjoc.20.100

• with excellent properties as organic photovoltaic materials [9][10][11][12][13][14]. Furthermore, regioisomerically pure bis-functionalized fullerenes function better as electron acceptors in organic thin-film solar cells than mixtures of the corresponding regioisomers do [12][13][14]. Therefore

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction

• Manoel T. Rodrigues Jr.,
• Aline S. B. de Oliveira,
• Ralph C. Gomes,
• Amanda Soares Hirata,
• Lucas A. Zeoly,
• Hugo Santos,
• João Arantes,
• Catarina Sofia Mateus Reis-Silva,
• João Agostinho Machado-Neto,
• Leticia Veras Costa-Lotufo and
• Fernando Coelho

Beilstein J. Org. Chem. 2024, 20, 1167–1178, doi:10.3762/bjoc.20.99

• 3-aryl-1-indanones) in good to excellent yield. The reaction did not require additives and was insensitive to both air and moisture. Preliminary biological evaluation of some indanones showed a promising profile against some human cancer line cells. Keywords: bismuth; catalysis; heterocycles

• ] and the broad spectrum of biological activities. Among the five-membered ring compounds, we find indanone (1, Figure 1). Within the class of indanones, we can highlight some interesting compounds. For example, nakiterpiosinone (2), which inhibits the growth of P388 mouse leukemia cells with an average

• tumor lines, HCT116 (colon adenocarcinoma), MCF7 (breast adenocarcinoma), SK-MEL-28 (melanoma), and NB4 (acute leukemia) by methylthiazol tetrazolium (MTT) assay, as previously described [85]. Among the tested cells, NB4 cells were the most sensitive ones, with 7 compounds (10aa,bk and 11aa,ad,ae,dc,bj