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

• –maleimide–PEG into their LNPs to target epidermal growth factor receptor (EGFR)-positive cancer cells. The authors showed an increased delivery of siRNAs and fluorescent quantum dot nanocrystals both in vitro and in EGFR-positive tumor xenografts in mice [48]. In 2020, Chandra et al. used a maleimide–PEG in

• their LNP formulation to functionalize LNPs with an aptamer specific for the human epidermal growth factor 2 (HER2) receptor. Therein, functionalized LNPs increased siRNA delivery and subsequent sensitivity of the doxorubicin-resistant HER2-positive breast cancer cell lines by ≈2-fold over LNPs with no

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• longer reaction time (3 h) with lower yields (60%) as compared to microwave (20 min with 91% yield). The library of molecules synthesized was found to be active against SKOV-3 cancer cells with 9a emerging as a promising molecule with IC50 = 0.24 ± 0.05 μM (Scheme 3). The protocol surfaces the efficiency

• subjecting them to the potential dipolarophile but-2-ynedionates to deliver the target molecules. Both the reactions proceeded well in water aiding in greener synthesis of biologically active molecules. The synthesized molecules exhibited significant activity against human lung cancer cell line A549. A

• cancer cell lines along with good antimicrobial activity (Scheme 24). The proposed mechanism (Scheme 25) involved a Knoevenagel condensation between aldehyde 5 and malononitrile (51) to form arylidene intermediate A. Then A reacts with isocyanide 21 to produce intermediate B which coordinates with 1,10

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

• +{FAM} ON and it was only present in the cytoplasm. These results indicate that ONs with phosphate modifications such as N+ or Ts might be suitable tools for the application of DNA and RNA vaccines [60], for the treatment of cancer [61], infectious diseases [62], and neurological disorders [63

• . Maksim V. Kvach for valuable discussions and suggestions. We also thank Mr. Raoul Solomon for assistance in the preparation of Figure 3 and Figure 4. Funding V.V.F. and Y.S. are grateful for the financial support provided by the School of Fundamental Sciences (Massey University) and Cancer Society of New

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

• ganglioside biosynthesis, and altered ganglioside status in cancer, and the effects on network structure are predicted. The simulator is available at the Glycologue website, https://glycologue.org/. Keywords: gangliosides; Glycologue; glycosyltransferases; neuropathy; Svennerholm nomenclature; Introduction

• disorders of ganglioside biosynthesis can lead to a number of neuropathies, including motor deficits, microcephaly, sensory loss, and autistic features [10][11]. Certain gangliosides, such as GM2, have been identified as tumor markers for breast cancer stem cells [12], while members of the alpha-series

Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity

• Zbigniew Malinowski,
• Emilia Fornal,
• Agata Sumara,
• Renata Kontek,
• Karol Bukowski,
• Beata Pasternak,
• Dariusz Sroczyński,
• Joachim Kusz,
• Magdalena Małecka and
• Monika Nowak

Beilstein J. Org. Chem. 2021, 17, 558–568, doi:10.3762/bjoc.17.50

• production [11] that plays an important role in the growth of various cancerous tissues (colon, lung, and breast cancer) and as antagonists of the human A3 adenosine receptor [12]. Aminophthalazines have been also evaluated for their inhibitory activity toward phosphodiesterases such as PDE-5 (Figure 1) [13

• cytotoxicity, proliferation and growth of HT-29 (human colon adenocarcinoma cell line), PC-3 (human prostate cancer cell line) and L-929 cells (mouse fibroblast cell line). The results obtained from the MTT assay revealed that the tested phthalazinone derivatives were cytotoxic towards the tested cell lines in

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• a low (1 mol %) catalyst loading, to obtain enantiomerically enriched β-naphthyl-β-sulfanyl ketones with up to 96% ee. The target adducts are the core structure of seco-raloxifene derivatives, which are potent anti-breast cancer agents [32]. In addition, the same scaffold has also shown urease

• , which have potent activity against breast cancer. The easy access to the corresponding sulfones presents a versatile route for the implementation of a new biologically active moiety, the sulfone, to the β-naphthyl-β-sulfanyl ketones. The enantioenriched products of both classes can be evaluated as

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

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• cytotoxic against a variety of cancer cell lines, and both bohemamine and NP25302 inhibit HL-60 cell adhesion to Chinese hamster ovary cells expressing intercellular adhesion molecule ICAM-1 (CD-54). This interest led us to develop a total synthesis of NP25302 [25] and its 5-normethyl analog and, as

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

• investigated in the presence of cell extracts. Ojima and collaborators have also employed functional ligand-observed NMR experiments to develop a range of novel 3′-difluorovinyltaxoids, such as BLT-F2 and BLT-S-F6 (Figure 5c), that are active against drug-sensitive and multidrug-resistant (MDR) human cancer

• presence of DNA, and another intrinsically disordered binding partner, breast cancer antigen 1 (BRCA1) (Figure 12). In this work the strategy employed involved the introduction of a perfluorinated [19F]3,5‐bis(trifluoromethyl)benzyl-based tag into the single cysteine residue of Myc. This modification

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

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

• 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

Control over size, shape, and photonics of self-assembled organic nanocrystals

• Chen Shahar,
• Yaron Tidhar,
• Yunmin Jung,
• Haim Weissman,
• Sidney R. Cohen,
• Ronit Bitton,
• Iddo Pinkas,
• Gilad Haran and
• Boris Rybtchinski

Beilstein J. Org. Chem. 2021, 17, 42–51, doi:10.3762/bjoc.17.5

• Current address: Center for Cancer Immunotherapy, La Jolla Institute for Immunology, La Jolla, CA, U.S.A. Department of Chemical Research Support, Weizmann Institute of Science, Rehovot 76100, Israel Department of Chemical Engineering, Ben-Gurion University, Beer Sheva 84105, Israel Ilse Katz Institute

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

• fundamental in proteomics, and the identification of PPIs has the potential to confer new drug targets for diseases, such as cancer. As a result, research involving PPIs is imperative for our biological knowledge and future aspects in medicine. Different methodologies employed to study PPIs. The protein used

Chemical constituents of Chaenomeles sinensis twigs and their biological activity

• Joon Min Cha,
• Dong Hyun Kim,
• Lalita Subedi,
• Zahra Khan,
• Sang Un Choi,
• Sun Yeou Kim and
• Chung Sub Kim

Beilstein J. Org. Chem. 2020, 16, 3078–3085, doi:10.3762/bjoc.16.257

• effects including cytotoxicity against cancer cell lines, antineuroinflammatory activity, and potential neurotrophic effect were evaluated. Keywords: antineuroinflammation; Chaenomeles sinensis; cytotoxicity; megastigmane; neurotrophic effect; Introduction Chaenomeles sinensis (Thouin) Koehne (Rosaceae

• . Cytotoxicity of compounds 9–11 against four cultured human cancer cell lines in the SRB bioassay. Inhibitory effects of compounds 1–12 on the NO production in LPS-activated BV-2 cells. Effects of compounds 1–12 on the NGF secretion in C6 cells. Supporting Information Supporting Information File 398: 1D and 2D

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

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

• involved in a variety of human diseases like cancer, Alzheimer’s, and Parkinson diseases etc. [46]. Therefore, the Schmuck group in collaboration with the Ottmann group sought to develop fluorescent probes (7 and 8) for monitoring of 14-3-3 proteins (Figure 7) [47]. These probes contain two symmetric GCP

Fluorine effect in nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-D-hexopyranose

• Danny Lainé,
• Vincent Denavit,
• Olivier Lessard,
• Laurie Carrier,
• Charles-Émile Fecteau,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2020, 16, 2880–2887, doi:10.3762/bjoc.16.237

• ; polyfluorinated carbohydrates; polyfluoroalditol analogues; Introduction The biological significance of carbohydrates includes, but are not limited to, immune regulation, infection, and cancer metastasis. Research in the field of molecular biology allowed the discovery of glycomimetics to study various

One-pot multicomponent green Hantzsch synthesis of 1,2-dihydropyridine derivatives with antiproliferative activity

• Giovanna Bosica,
• Kaylie Demanuele,
• José M. Padrón and
• Adrián Puerta

Beilstein J. Org. Chem. 2020, 16, 2862–2869, doi:10.3762/bjoc.16.235

• preliminary study of the antiproliferative activity against human solid tumor cells demonstrated that 1,2-DHPs could inhibit cancer cell growth in the low micromolar range. Keywords: antiproliferative activity; 1,2-dihydropyridines; green Hantzsch synthesis; heterogeneous catalysis; one-pot multicomponent

• the general procedure. Biological screening The 1,4-DHP scaffold displays an extensive range of biological activities, including reversing multidrug resistance (through the inhibition of the P-glycoprotein) [26] and antiproliferative effects on human cancer cell lines [27]. We wondered whether the

• , the reaction was left to carry on but stopped, and therefore catalyst leaching was not evident. Antiproliferative tests We selected the cancer cell lines A549 and SW1573 (nonsmall-cell lung), HBL-100, as well as T-47D (breast), HeLa (cervix), and WiDr (colon) to evaluate the antiproliferative activity

Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives

• Jonas Becher,
• Daria V. Berdnikova,
• Heiko Ihmels and
• Christopher Stremmel

Beilstein J. Org. Chem. 2020, 16, 2795–2806, doi:10.3762/bjoc.16.230

• several human cancer cells, but has only a relatively low cytotoxicity in healthy cells [31][32]. Berberine is also known as a G4-DNA ligand [33]. Especially berberine derivatives that carry additional substituents with varying alkyl chain lengths in the 9- and 13-position show enhanced binding properties

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

• reversibly change the properties of the cell. For example, we have shown that synthetic receptors appended with a thiol or a folate group enable bacteria expressing the His-tagged outer membrane protein C (His-OmpC) to bind to gold surfaces or cancer cells, respectively [2]. We have also shown that this

Enzyme-instructed morphological transition of the supramolecular assemblies of branched peptides

• Dongsik Yang,
• Hongjian He and
• Bing Xu

Beilstein J. Org. Chem. 2020, 16, 2709–2718, doi:10.3762/bjoc.16.221

• , peptide assemblies are being explored for a wide range of applications, including cell cultures [6], tissue engineering [7], drug delivery [8][9][10][11], antibacterial agents [12][13], regarding biomineralization [14][15], as collagen mimics [16], anisotropic hydrogels [17][18], for cancer therapy [19

Comparative ligand structural analytics illustrated on variably glycosylated MUC1 antigen–antibody binding

• Christopher B. Barnett,
• Tharindu Senapathi and
• Kevin J. Naidoo

Beilstein J. Org. Chem. 2020, 16, 2540–2550, doi:10.3762/bjoc.16.206

• epithelial cancers [8]. Further, it is thought to participate in the hyperactivation of selected intracellular signal transduction pathways that promote tumorigenicity [9]. MUC1 is a cancer biomarker that can be detected by serum biomarker assays (such as the CA15-3 test [10][11]). The mode of binding

• epithelial cells, the mixture of O-glycans that glycosylate mucins are extended core 2 structures, while in breast cancer cells, O-glycan mass decreases (hypoglycosylation), and there is an increase in abundance of sialylated core 1 [15]. The upregulation of Tn (αGalNAc) and STn (αNeuAc-2,6-αGalNAc) antigens

• breast cancer [11][13]. We use MD simulations to investigate the conformational behavior of (glyco)peptide antigens bound to the AR20.5 antibody and to investigate the hypothesis that the glycan modulates the conformation of the peptide portion of the antigen. Primarily showcasing a structural analytics

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• cancer cell growth. Ruthenium(II) tris(bipyridine) (RuII(bpy)3) complexes carrying multiple carboxylate-substituted arms were designed as protein surface mimetics, exploiting electrostatic binding through multiple contacts to the protein surface [63]. 15N-HSQC titrations showed that these complexes

Tools for generating and analyzing glycan microarray data

• Akul Y. Mehta,
• Jamie Heimburg-Molinaro and
• Richard D. Cummings

Beilstein J. Org. Chem. 2020, 16, 2260–2271, doi:10.3762/bjoc.16.187

• blood group antigens (A, B, O), which are glycan structures found on blood cells and tissues that play a critical role in determining transfusion compatibility during blood and organ donation [3], sialyl-LewisA antigen, known more commonly as CA19-9, which is a known tumor marker for pancreatic cancer

• , and could possibly promote cancer [4], and the O-glycan of PSGL-1 which is recognized by P- and L-selectin, which is critical for leukocyte recruitment [5][6]. Other roles of glycans (including glycosaminoglycans/proteoglycans) and glycan binding proteins (GBPs) (including lectins and antibodies) in

• biological systems have been discovered with respect to cancer, infectious diseases, and genetic disorders [7][8][9][10][11][12][13][14][15]. As a technology to study glycan recognition by GBPs, glycan microarrays offer an invaluable tool, and permit examination of all types of lectins, along with antibodies

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• atoms, including drugs used to treat cancer, HIV, smallpox and malarial infections (Figure 1) [5][6]. Moreover, fluorine atoms and trifluoromethyl groups have dramatic effects on the biological activity of agrochemicals, such as herbicides, insecticides and fungicides, as reflected by a plethora of

GlypNirO: An automated workflow for quantitative N- and O-linked glycoproteomic data analysis

• Toan K. Phung,
• Cassandra L. Pegg and
• Benjamin L. Schulz

Beilstein J. Org. Chem. 2020, 16, 2127–2135, doi:10.3762/bjoc.16.180

• Fisher) and Byonic (Protein Metrics), to extract occupancy and glycoform abundancy of all identified glycopeptides from LC–MS/MS datasets. We applied the workflow to a published dataset comparing the plasma glycoproteomes of liver cancer patients (heptatocellular carcinoma, HCC) and healthy controls [20

• depleted of six abundant proteins from liver cancer (hepatocellular carcinoma (HCC)) patients and healthy controls. We identified glycopeptides and peptides in the datafiles from these samples using Byonic, searching separately for O- and N-glycopeptides (Supporting Information File 1, Tables S1–S24), and