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

•  3A) [57]. The G-clamp modification was later observed to have antisense inhibition activity involving RNase H cleavage with a single incorporation into a PS-ON [58]. Afterwards, a guanidino-G-clamp (modification 24) was synthesized to increase the number of hydrogen bonds that could be established

• for the modified TFO to work effectively, thus demonstrating the significance of sequence-specific binding. It was however important that the TFO and plasmid were mixed prior to injection, to get near-complete inhibition of gene expression. Only partial inhibition could be observed, if TFOs were

• injected before the plasmid, and no inhibition could be observed when the plasmid was injected first. This indicated that a competition between the cationic TFOs and the histones for DNA binding had a large impact [111]. The library of phosphoramidate variants was expanded when the aminobutyl

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• ACAT2 and renders it inactive [173]. In vivo, PPPA-mediated ACAT2 inhibition was shown to protect the mice from atherosclerosis, ACAT2 enzyme mediates in lipid metabolism and is localized in the liver and intestines [174]. Furthermore, PPPA was also shown to exhibit insecticidal properties against

Cerium-photocatalyzed aerobic oxidation of benzylic alcohols to aldehydes and ketones

• Girish Suresh Yedase,
• Sumit Kumar,
• Jessica Stahl,
• Burkhard König and
• Veera Reddy Yatham

Beilstein J. Org. Chem. 2021, 17, 1727–1732, doi:10.3762/bjoc.17.121

• inhibition of the catalytic cycle upon the addition of TEMPO revealed that the reaction proceeds through radical intermediates. Next, we carried out UV–vis monitoring experiments in order to verify whether the interaction with the substituted benzyl alcohols and CeIV could lead to a ligand-to-metal charge

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

• any Watson–Crick base pairing scheme, AOVP lowered the stability of PNA duplexes with complementary DNA and RNA [132]. Similarly, vinyl-modified purine (AVP) effectively crosslinked with thymine in DNA and with uracil in RNA. The crosslinking resulted in inhibition of Dicer processing of microRNA

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• substituted methylene linkage. Biological studies have shown that this toxin is responsible for “quick disease” (gousiekte) in ruminant animals, which causes inhibition of protein synthesis in the cardiovascular organs [13]. The unique structure coupled with the biological effects of this polyamine prompted

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

• the oral cavity. The inhibition efficacy of dsRNAvp28 to WSSV by oral route was evaluated using free dsRNAvp28 and VLP-dsRNAvp28 administered directly into the shrimp’s oral cavity. The procedure was standardized before the bioassay. In summary, 50 µL of TN solution containing 10% red food coloring

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

• compound (+)-L-733,060 (140), a potent neurokinin substance P receptor antagonist. This compound displays a wide variety of biological activities, including inhibition of neurogenic inflammation, blocking of pain transmission and regulation of immune response (Scheme 38). A stereoselective synthesis of ʟ

Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• ) [49] and insulin (a2) [50], or in telomerase inhibition (F21T) [30][51][52]. At a ligand-DNA ratio (LDR) of 5, the derivatives 5b–e induced a small, but significant shift of the melting temperature of the oligonucleotides F21T (∆Tm = 1.8–3.9 °C), and FmycT (∆Tm = 1.3–2.1 °C), while the melting

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• involved in TGFβ inhibition [142]. The inclusion of LNA nucleosides within a larger single-stranded DNA oligonucleotide has also allowed for subtle gene modifications to be implemented while evading mismatch repair (MMR) [143]. Furthermore, Ju et al. recently reported the use of LNA-based suppressors for

• the inhibition of viral miRNA through carbon dot-mediated delivery [144]. A diastereomer of LNA, α-ʟ-LNA (Figure 7B), also induces a higher affinity for both DNA and RNA complements in addition to providing a high stability against nucleases [145][146]. Unlike LNA, this diastereomer is a mimic of DNA

Simulating the enzymes of ganglioside biosynthesis with Glycologue

• Andrew G. McDonald and
• Gavin P. Davey

Beilstein J. Org. Chem. 2021, 17, 739–748, doi:10.3762/bjoc.17.64

• memory formation through neuromodulation of synaptic transmission [8]. Gangliosides are recycled in the lysosome through the action of glycohydrolases. The inhibition of membrane recycling has been shown to lead to an accumulation of lysosomal gangliosides resulting in neuronal death [9]. Congenital

Synthesis of dibenzosuberenone-based novel polycyclic π-conjugated dihydropyridazines, pyridazines and pyrroles

• Ramazan Koçak and
• Arif Daştan

Beilstein J. Org. Chem. 2021, 17, 719–729, doi:10.3762/bjoc.17.61

• commonly used for the synthesis of biologically active compounds having enzyme inhibition and antiviral activity [1][2], and are found in the structures of many commercially available antidepressant drugs [3][4][5][6][7][8][9][10][11][12]. In addition, dibenzosuberenone (1) and polyconjugated derivatives

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes

• Zafar Iqbal,
• Lijuan Zhai,
• Yuanyu Gao,
• Dong Tang,
• Xueqin Ma,
• Jinbo Ji,
• Jian Sun,
• Jingwen Ji,
• Yuanbai Liu,
• Rui Jiang,
• Yangxiu Mu,
• Lili He,
• Haikang Yang and
• Zhixiang Yang

Beilstein J. Org. Chem. 2021, 17, 711–718, doi:10.3762/bjoc.17.60

• vitro. All compounds did not show antibacterial activity when tested alone (MIC >64 mg/L), however, they exhibited a moderate inhibition activity in the presence of meropenem by lowering its MIC values. The compound A12 proved most potent among the other counterparts against all bacterial species with

• in Escherichia coli clinical isolates [14][15]. The diazabicyclooctane (DBO) [16] ring suggested as an alternative to the β-lactam ring [17] by the Hoechst researchers [16] could not prove its antibacterial strength in early experiments rather it showed β-lactamase inhibition activity. This discovery

• , indicating a racemization during the reaction process. The less polar isomer with R-configuration [31][32] at C2 showed a complete loss of β-lactamase inhibition activity as compared to the more polar isomer. Therefore, the less polar isomer was discarded while saving the more polar S-isomer, (relative ratio

Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

• Marek Kõllo,
• Marje Kasari,
• Villu Kasari,
• Tõnis Pehk,
• Ivar Järving,
• Margus Lopp,
• Arvi Jõers and
• Tõnis Kanger

Beilstein J. Org. Chem. 2021, 17, 581–588, doi:10.3762/bjoc.17.52

• Pseudopterogorgia americana in 1972 (Figure 1B) [7], several others from the family have been reported [8][9][10][11][12][13][14]. The 9,11-secosterols exhibit diverse biological activities, including antihistaminic, antiproliferative, anti-inflammatory, cytotoxic and protein kinase C (PKC) inhibition activities [8

Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs

• Kenji Morokuma,
• Shuntaro Tsukamoto,
• Kyosuke Mori,
• Kei Miyako,
• Ryuichi Sakai,
• Raku Irie and
• Masato Oikawa

Beilstein J. Org. Chem. 2021, 17, 540–550, doi:10.3762/bjoc.17.48

• subgram quantities of (rac)-MC-27 ((rac)-4), which was found to cause weak inhibition of the voluntary movement of mice upon intracerebroventricular injection [5]. On the basis of the racemate synthesis shown in Scheme 1, in the present study, we envisioned that both enantiomers of MC-27 could

• /mouse) of (2R)-MC-27 (4) caused a weak inhibition of the voluntary action of the mouse, which had been observed previously with (rac)-MC-27 with a nearly identical potency [5]. Therefore, it was concluded that the (2R)-enantiomer is responsible for the neuroactivity of (rac)-MC-27. On the other hand

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• R2 substituent tolerance. Moreover, in order to demonstrate the application potential of our method, a few more derivatives containing R2: I instead of Cl (5ac’, 5cc’, 5dc’) which display a significant kinase inhibition activity, have been prepared. It is worth noting that the existing literature

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

• catabolic degradation of proline plays an important role in the development of cancer cells, making the inhibition of the proline dehydrogenase a promising method in cancer therapy [69][70]. There is no information on a possible intracellular degradation of fluoroprolines, although, they are included in

• some therapeutic dehydrogenase inhibition schemes [71]. Conversely, there is strong evidence that other proline analogues, dehydroproline and thiaproline, are oxidatively degraded in E. coli by the action of the bifunctional enzyme putA and the reductase proC [72]. Future research should examine

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

• estrogen receptor (ER) co-activator peptides and enabled the sensitive detection of their protein–peptide interaction inhibition by the ER antagonist tamoxifen [20]. Significantly, different secondary structure conformational preferences were also found among the diastereomers of perfluoro-tert

• biosynthesis through hBBOX-catalysed GBBNF hydroxylation, both in vitro and in cell lysates [43]. Moreover, by using a competitive substrate for the enzyme, inhibition experiments could be directly employed to determine the IC50 values in the basis of fluoride release, and the extent of GBBNF turnover

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

• (Scheme 1) [12]. In 2011, a single example of a C6-phosphonate, B (X = NH2; R1 = 2’-C-methylribose; R2 = Et), was synthesized among other compounds as a potential anti-hepatitis C virus agent and showed 19% inhibition at 10 μM in Huh7 cells (Scheme 1) [13]. Additionally, there are a few examples of C8

Insight into functionalized-macrocycles-guided supramolecular photocatalysis

• Minzan Zuo,
• Krishnasamy Velmurugan,
• Kaiya Wang,
• Xueqi Tian and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2021, 17, 139–155, doi:10.3762/bjoc.17.15

• , during the catalytic process, the reactive guest should have a greater binding affinity or the photoproducts should have the lowest binding affinity with the supramolecular host to avoid product inhibition, so as to produce a better catalytic turnover efficiency [14][15]. However, it is quite complicated

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

• Michał M. Więcław and
• Bartłomiej Furman

Beilstein J. Org. Chem. 2021, 17, 115–123, doi:10.3762/bjoc.17.12

• ones in this work – fused iminosugar-tetrazoles – which have shown inhibition properties against bovine liver α-ᴅ-glucuronidase and human β-ʟ-iduronidase [29]. Moreover, there are numerous reports of the organocatalytic activity of chiral aminotriazoles and aminotetrazoles in number of reactions, such

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• Omura’s group in 1995 [3]. Inthomycin A ((+)-1) displays moderate antifungal activity against cellulose-containing Phytophthora parasitica and Phytophthora capsici [4]. Inthomycins were reported to possess many interesting biological properties, which include the specific inhibition of the cellular

• biosynthesis [1][4], in vitro antimicrobial activity [4][5], and anticancer activity against human prostate cancer cell lines [6][7]. A recent study suggested that the close analogue (+)-11 of inthomycin C was found to exhibit proteasome inhibition activity [8]. The skeletal structures of inthomycins A–C (1–3

Molecular basis for protein–protein interactions

• Brandon Charles Seychell and
• Tobias Beck

Beilstein J. Org. Chem. 2021, 17, 1–10, doi:10.3762/bjoc.17.1

• functionality and the corresponding pathways. Important roles of PPIs include hormone reception [2], protease inhibition [3], antibody–antigen complexes [4], gene regulation [5], and large biomolecular assemblies [6]. PPI identification and prediction are important for targeting anticancer strategies [7

Secondary metabolites of Bacillus subtilis impact the assembly of soil-derived semisynthetic bacterial communities

• Heiko T. Kiesewalter,
• Carlos N. Lozano-Andrade,
• Mikael L. Strube and
• Ákos T. Kovács

Beilstein J. Org. Chem. 2020, 16, 2983–2998, doi:10.3762/bjoc.16.248

• , enzyme inhibition, or disruption of bacterial protein synthesis. This knowledge was primarily acquired in vitro when B. subtilis was competing with other microbial monocultures. However, our understanding of the true ecological role of these small molecules is limited. In this study, we have established

• indicated that the genus Lysinibacillus was negatively affected by the addition of B. subtilis P5_B1 WT and that NRPs enhance the suppression. To dissect the direct impact of a particular NRP in this inhibition, we monitored the growth of L. fusiformis M5, a previously isolated Lysinibacillus species [54

• in the exponential growth phase. Furthermore, the effect of spent WT medium seems to be reduced at this concentration, but the spent media of ∆ppsC and ∆pksL maintained their growth inhibition potential. The lowest concentration of a spent medium having an inhibitory effect was 10.02%. At this

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

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

• ). The inhibition by peptide 9 is found to be in a reversible and noncompetitive way. Molecular modeling shows four cationic ammonium groups forming ion pairs and hydrogen bonds with negatively charged residues, such as Glu217, Asp60B, Asp147 and Glu217, respectively and completely block the central pore

Ultrasound-assisted Strecker synthesis of novel 2-(hetero)aryl-2-(arylamino)acetonitrile derivatives

• Emese Gal,
• Luiza Gaina,
• Hermina Petkes,
• Alexandra Pop,
• Castelia Cristea,
• Gabriel Barta,
• Dan Cristian Vodnar and
• Luminiţa Silaghi-Dumitrescu

Beilstein J. Org. Chem. 2020, 16, 2929–2936, doi:10.3762/bjoc.16.242

• ), or sodium azide (known mutagen for TA 100), was also examined using the plate incorporation procedure and the results are summarized in Table 2 and Table 3. This assay proved a strong antimutagenic activity of all tested α-(arylamino)acetonitrile derivatives, with a better inhibition exhibited in the

• case of the TA98 strain (44–95%), but nevertheless considerable for TA100 strain (46–79%). The results of the antimutagenicity assay indicate a lower inhibition exhibited in the presence of liver homogenate (S9), pointing out that metabolizing enzymes could interfere with the activation of the