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

• 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

• the properties of ONs, i.e., enzymatic stability, hybridization, biodistribution, and cell-uptake, via the introduction of non-natural internucleoside linkages. The most well-known modification is the phosphorothioate-linked backbone, which is known to enhance not only nuclease resistance but also

• /bovine serum at 37 °C for 8 h. Here, a significant improvement over the unmodified 2’-OMe RNA was observed for modification 81 [115]. The two BCNSs used for monomers 79–81 (1,3-bis(2-(amino)ethoxy)-2-propyl and bis(2-(dimethylamino)ethoxy)-2-propyl) were tested for their cell uptake properties. The BCNS

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• cancer cells. Keywords: γ-carboline; cascade reaction; cell uptake; cytotoxicity; fluorescence; Introduction Carbolines are privileged aza-heterocycles found in the core of several natural and synthetic compounds and are known for their biological applications. Among the four different isomers, 9H

• studies show that the γ-carbolines are highly toxic to cancer cells at micromolar concentrations similar to doxorubicin, whereas they are non-cytotoxic (Figure 6) to human macrophages or immune cells. At last, to evaluate cell uptake of the novel γ-carboline for fluorescence imaging, live-cell imaging

• Software, San Diego, CA). HeLa cell uptake study of γ-carboline 3ac A live-cell imaging experiment was performed with HeLa cells. The HeLa cells were placed in a 4-well confocal dish (cell count ≈ 100 cells per well) and incubated for 48 h at 37 °C under 5% CO2. After 3 h of incubation with carboline

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

• % increase in cellular uptake through the BBB and into target cells and that these cells had higher LNP uptake (measured by a higher MFI) than the non-antigen-expressing counterparts, while the gp160 aptamer (A-1) had no apparent effect on target cell uptake. One could speculate that this may be the result

• [22]. In 1997 and 2002, Kircheis et al. developed a polyethyleneimine (PEI)-conjugated transferrin molecule at a ratio of PEI/transferrin 21.4 nmol:270 nmol and observed that transferrin shielded the PEI, decreasing toxicity and increasing target cell uptake through binding to the transferrin receptor

DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

• Yongdong Su,
• Maitsetseg Bayarjargal,
• Tracy K. Hale and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2021, 17, 749–761, doi:10.3762/bjoc.17.65

• responsible for the stabilisation of duplexes with N+ modification. N+ONs also demonstrated greater resistance to nuclease digestion by snake venom phosphodiesterase I than the corresponding Ts-ONs. Cell uptake studies showed that Ts-ONs can enter the nucleus of mouse fibroblast NIH3T3 cells without any

• transfection reagent, whereas, N+ONs remain concentrated in vesicles within the cytoplasm. These results indicate that both N+ and Ts-modified ONs are promising for various in vivo applications. Keywords: cell uptake; charge neutral modification; DNA; modified phosphates; Staudinger reaction; Introduction

• phosphate backbone of DNA and RNA, especially charge neutral modifications, have gained attention in recent years because such modifications not only improve the nuclease resistance of ONs but also enhance their affinity towards complementary DNA/RNA/dsDNA and improve cell uptake. The lack of a negatively

Archangelolide: A sesquiterpene lactone with immunobiological potential from Laserpitium archangelica

• Silvie Rimpelová,
• Michal Jurášek,
• Lucie Peterková,
• Jiří Bejček,
• Vojtěch Spiwok,
• Miloš Majdl,
• Michal Jirásko,
• Miloš Buděšínský,
• Juraj Harmatha,
• Eva Kmoníčková,
• Pavel Drašar and
• Tomáš Ruml

Beilstein J. Org. Chem. 2019, 15, 1933–1944, doi:10.3762/bjoc.15.189

• described natural compound archangelolide (1) and its fluorescent dansyl conjugate 5 in primary, cancer and primary immune cells. First, we analyzed the rate of cell uptake of compound 5 and dansyl amide in U-2 OS (Figure 2 and Supporting Information File 1, Figure S18) and MRC-5 (Supporting Information

• overnight in triplicates, treated with the tested compounds and incubated for another 24 h. The amount of WST-1 was 10 µL per 100 µL of media and the incubation took 3 h. The results are expressed as the percentage of cytotoxicity relative to 100% of dead cells treated with 1% Triton X-100. Cell uptake

• in section “Cell uptake study”. To assess the intracellular localization of compound 5 in MRC-5 cells, an endoplasmic reticulum marker ER-Tracker™ Red (120 nM, 30 min; ThermoFisher Scientific, USA) and a mitochondria-specific dye (70 nM, 30 min; UCT Prague, CZ) from [20] were used. In U-2 OS cells

Complexation of a guanidinium-modified calixarene with diverse dyes and investigation of the corresponding photophysical response

• Yu-Ying Wang,
• Yong Kong,
• Zhe Zheng,
• Wen-Chao Geng,
• Zi-Yi Zhao,
• Hongwei Sun and
• Dong-Sheng Guo

Beilstein J. Org. Chem. 2019, 15, 1394–1406, doi:10.3762/bjoc.15.139

• ][27][58]. Nau and co-workers reported a SC4A–lucigenin IDA system to monitor the cell-uptake efficiencies of choline, acetylcholine and protamine [58]. Also, we reported a non-covalent fluorescence switch-on strategy for hypoxia imaging in cancer cells by utilizing the complex of a carboxyl-modified

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• modeling study. In general, bisbenzimidazole derivatives (conjugate 57) exhibit much better antibacterial activity than mono-benzimidazoles for Gram-positive strains. More importantly, the linker lengths and composition have dramatic influence on DNA binding and cell uptake, suggesting that the roles of

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• diminishing expressed nucleoside receptors responsible for the cell uptake of gemcitabine [6]. Additionally, chemotherapy with anticancer agents is often hampered by their poor aqueous solubility, low oral bioavailability and metabolic instability. These drawbacks are linked to the unfavorable ADME

Development of novel cyclic NGR peptide–daunomycin conjugates with dual targeting property

• Andrea Angelo Pierluigi Tripodi,
• Szilárd Tóth,
• Kata Nóra Enyedi,
• Gitta Schlosser,
• Gergely Szakács and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 911–918, doi:10.3762/bjoc.14.78

• . All the degradation mixtures were kept at 37 °C, samples of 13 µL were taken at 0 h, 6 h and 72 h. Reaction mixtures were quenched by the addition of 2 µL of formic acid. LC–MS analysis was performed at the end on each sample. Cell uptake Analogous to the description in [17], prior to the treatment

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• such as gene regulation is to circumvent the poor chemical stability of nucleic acids in biological media due to their low resistance to nucleases and to overcome their low cell uptake due to their polyanionic nature. In the present review, we aimed to identify various ON prodrugs that are responsive

• phosphotriester ONs is rather poor [29], the design of ONs combining phosphodiester and phosphotriester linkages is required to ensure aqueous solubility and sufficient lipophilicity for cell uptake. Several attempts to obtain such chimeras were made in Imbach’s laboratory in the early 2000s. In particular, the

Correction: Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 1136–1138, doi:10.3762/bjoc.13.112

• polysaccharide-derived CDs in the presence of PEG-200 and how the starting material composition is conferred to the CD products. Corrected Scheme 22 of the original article. Hyaluronic acid (HA) and glycine-derived CDs, suspected to be decorated in unreacted HA, allowing receptor-mediated cell uptake.

Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 675–693, doi:10.3762/bjoc.13.67