p-tert-Butylthiacalix[4]arenes functionalized by N-(4’-nitrophenyl)acetamide and N,N-diethylacetamide fragments: synthesis and binding of anionic guests

• Alena A. Vavilova and
• Ivan I. Stoikov

Beilstein J. Org. Chem. 2017, 13, 1940–1949, doi:10.3762/bjoc.13.188

• in the regulation of anions is a cause of many diseases [7][8][9][10][11][12]. Thus, selective synthetic receptors can be used in medicine as medicinal and diagnostic agents. However, the design and synthesis of the systems for recognizing anions remains one of the important scientific challenges in

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• ]. While N-WASP is ubiquitously expressed, WASP is only found in cells of the hematopoietic lineage and appears to be critically involved in the regulation of the immune system [95]. WASP and N-WASP exist in a basal auto-inhibited state, a closed conformation in which the C-terminal verprolin homology

• -treated cells die by apoptosis. Interestingly, the addition of wiskostatin, which was previously shown to counteract cytotoxic effects of mycolactones [93], even enhanced mycolactone toxicity. By using a real-time PCR (qPCR) screening of 84 genes involved in the regulation of apoptosis, autophagy and

• -regulation of Bim. Furthermore, the suggested interaction of mycolactone A/B with FKBP12 is supported by the protective effects of an excess of FK506 against mycolactone-induced apoptosis. However, further experimental validation of the mycolactone-FKBP12 interaction, e.g., by SPR, NMR or X-ray

Grip on complexity in chemical reaction networks

• Albert S. Y. Wong and
• Wilhelm T. S. Huck

Beilstein J. Org. Chem. 2017, 13, 1486–1497, doi:10.3762/bjoc.13.147

• connections, certain patterns of interconnections, so-called “network motifs”, are relatively common [23]. Hence, underneath the complexity, local regulation based on minimal systems comprises a fairly simple set of basic events (i.e., activation and inhibition). Minimal network motifs have the advantage of

• networks exhibiting oscillatory behavior. Within this framework, Figure 4b shows an in vitro implementation of an oscillator comprising a positive and a delayed negative feedback loop [90]. The canonical gene regulation pathway uses the information encoded in DNA templates T1−T3. Similarly, a genetic

• predator–prey network. Adapted with permission from [88], copyright 2013 American Chemical Society. (b) The gene regulation pathway and of an oscillator based on a positive and delayed negative feedback motif, with experimentally observed oscillations shown to be in good agreement with the simulations

From chemical metabolism to life: the origin of the genetic coding process

• Antoine Danchin

Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111

• construction of cells, as well as transport across membranes, movement for exploration (including predation), protection against accidents and management of competition, but also repair, sensing and regulation. Almost all of these actions are operated by proteins in extant living organisms. A major question

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• metallic NPs. Carbohydrate–carbohydrate interactions (CCIs), generally characterized by KD values in the millimolar range, are very difficult to detect. Updated data confirm the crucial role of these bindings in the regulation of many cellular processes [72], however, researches related to the use of

• -inflammatory response in dendritic cells via interaction with the lectin DC-SIGN, as indicated by the up-regulation of several maturation markers and increased secretion of pro-inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) [97]. These data indicate that a multivalent system of

• titers of specific IgG antibodies towards type 14 polysaccharide compared with GAuNP exclusively displaying Pn14. The GAuNP technology has also been applied in the regulation of important genes of the apoptotic pathway. New GAuNP systems displaying cMyc targeting siRNA resulted capable of inducing

Expression, purification and structural analysis of functional GABA transporter 1 using the baculovirus expression system

• Jing Hu,
• Chris Weise,
• Christoph Böttcher,
• Hua Fan and
• Jian Yin

Beilstein J. Org. Chem. 2017, 13, 874–882, doi:10.3762/bjoc.13.88

• mechanism as a common transport mechanism for the GAT1 protein [13][17][18][19][20]. Since the GABAergic system has been implicated in many nervous system diseases [21][22][23][24], the regulation of GABA activity is of considerable medical interest [25][26] and the predominant GABAergic nerve ending

• but not the terminal trimming of N-glycans is involved in the regulation of the correct membrane glycoprotein folding since the inhibition of N-glycosylation processing by 1-deoxymannojirimycin (dMM) results in a mannose-rich type of N-glycan that does not affect either the protein stability or

First total synthesis of kipukasin A

• Chuang Li,
• Haixin Ding,
• Zhizhong Ruan,
• Yirong Zhou and
• Qiang Xiao

Beilstein J. Org. Chem. 2017, 13, 855–862, doi:10.3762/bjoc.13.86

• ; Introduction Endogenous nucleosides are involved in DNA and RNA synthesis, cell signalling, enzyme regulation and metabolism etc. [1][2]. Therefore, the synthesis of novel nucleosides to mimic their physiological counterparts has potential therapeutic significance, which has led to the development of a large

Isoxazole derivatives as new nitric oxide elicitors in plants

• Anca Oancea,
• Emilian Georgescu,
• Florentina Georgescu,
• Alina Nicolescu,
• Elena Iulia Oprita,
• Catalina Tudora,
• Lucian Vladulescu,
• Marius-Constantin Vladulescu,
• Florin Oancea and
• Calin Deleanu

Beilstein J. Org. Chem. 2017, 13, 659–664, doi:10.3762/bjoc.13.65

• orchestration of various plant physiological responses, playing an important role in the regulation of interactions between plant and microorganisms and in plant defense mechanisms against stresses [18][19]. Consequently, there is interest in the biological evaluation of further isoxazole derivatives. Many

Investigation of the action of poly(ADP-ribose)-synthesising enzymes on NAD⁺ analogues

• Sarah Wallrodt,
• Edward L. Simpson and
• Andreas Marx

Beilstein J. Org. Chem. 2017, 13, 495–501, doi:10.3762/bjoc.13.49

• considered the main source of cellular PAR [11]. ARTD1 and its closest relative ARTD2 comprise DNA-binding domains and their activity is stimulated by binding to different types of DNA breaks [12]. They fulfil functions in DNA repair, genome maintenance, transcription, and metabolic regulation [11][13]. The

NMR reaction monitoring in flow synthesis

• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2017, 13, 285–300, doi:10.3762/bjoc.13.31

•  10). The design represented in Figure 10 allows the regulation of the molar ratio of reagents for the kinetic experiments (urea/formaldehyde from 1:1 to 4:1) as well as the temperature and pH, which were constantly measured. The reaction mixture flowed to the NMR instrument (400 MHz) by way of a pump

Versatile synthesis of the signaling peptide glorin

• Robert Barnett,
• Daniel Raszkowski,
• Thomas Winckler and
• Pierre Stallforth

Beilstein J. Org. Chem. 2017, 13, 247–250, doi:10.3762/bjoc.13.27

• were harvested and total RNA was extracted. The differential regulation of PPL_09347 was determined by RT-qPCR. Synthetic glorin (1) and glorinamide 2 led to similar expression of PPL_09347, comparable to commercial glorin as positive control (Figure 2). While a small baseline induction of PPL_09347

Synthesis of multi-lactose-appended β-cyclodextrin and its cholesterol-lowering effects in Niemann–Pick type C disease-like HepG2 cells

• Keiichi Motoyama,
• Rena Nishiyama,
• Yuki Maeda,
• Taishi Higashi,
• Yoichi Ishitsuka,
• Yuki Kondo,
• Tetsumi Irie,
• Takumi Era and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2017, 13, 10–18, doi:10.3762/bjoc.13.2

• of hearing loss due to its hepatocyte-selectivity. In order to evaluate the liver accumulation of multi-Lac-β-CD (DSL5.6), the biodistribution studies need to be performed in NPC disease model mice in future. The galactose density is a crucial factor for regulation of galactose affinity to ASGPR

Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

• Salvatore V. Giofrè,
• Santa Cirmi,
• Raffaella Mancuso,
• Francesco Nicolò,
• Giuseppe Lanza,
• Laura Legnani,
• Agata Campisi,
• Maria A. Chiacchio,
• Michele Navarra,
• Bartolo Gabriele and
• Roberto Romeo

Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278

• that plays a key role in the regulation of several cellular processes, including apoptosis, DNA repair, and angiogenesis [1][2][3][4]. The murine double minute 2 (MDM2) protein is the primary cellular inhibitor of p53, functioning through direct interaction with p53 [5]: tumoral cells show an

Chemical probes for competitive profiling of the quorum sensing signal synthase PqsD of Pseudomonas aeruginosa

• Michaela Prothiwa,
• Dávid Szamosvári,
• Sandra Glasmacher and
• Thomas Böttcher

Beilstein J. Org. Chem. 2016, 12, 2784–2792, doi:10.3762/bjoc.12.277

• disruption of AQ signaling and thereby to global down-regulation of virulence factor production [11]. Consequently, PqsD has become a highly attractive target and a great amount of work pioneered by the Hartmann group has resulted in inhibitor discovery using a combination of in vitro assay, in silico

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

• thaumatin, the regulation of the interaction of thaumatin with GPCRs is probably possible. Varca et al. published on the possible applications in the formulations of protein-like structures, such as enzymes, peptides and amino acids, for pharmaceutical applications [94]. The authors highlight that the

• macrophage accumulation, and thus help prevent or even regress atherosclerosis. The alteration of cellular cholesterol regulation, named the reverse cholesterol transport, RCT, could be used to block atheroprogression associated with different severity degrees of atherosclerosis pathogenesis. From the

Inhibition of peptide aggregation by means of enzymatic phosphorylation

• Kristin Folmert,
• Malgorzata Broncel,
• Hans v. Berlepsch,
• Christopher H. Ullrich,
• Mary-Ann Siegert and
• Beate Koksch

Beilstein J. Org. Chem. 2016, 12, 2462–2470, doi:10.3762/bjoc.12.240

• ATP was prepared and used to dissolve lyophilized KFM6. PKA is the most studied and structurally well-characterized protein kinase, and it is known to have relatively broad substrate specificity due to its roles in the regulation of energy metabolism, growth, signal transduction, and apoptosis of

Organic chemistry meets polymers, nanoscience, therapeutics and diagnostics

• Vincent M. Rotello

Beilstein J. Org. Chem. 2016, 12, 1638–1646, doi:10.3762/bjoc.12.161

• external regulation [4]. I also took on a brutal project, focused on the synthesis of water-soluble analogs of Kemp's triacid. This project was a massive effort, with a huge number of reactions required to optimize the initial steps. We did, however, obtain the desired receptors and observe some

Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

• Tai Nguyen Van,
• Audrey Hospital,
• Corinne Lionne,
• Lars P. Jordheim,
• Charles Dumontet,
• Christian Périgaud,
• Laurent Chaloin and
• Suzanne Peyrottes

Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144

• (cN-II), an enzyme involved in the regulation of purine nucleotide pools. NMR and molecular modelling studies showed that a few derivatives adopted similar structural features to IMP or GMP. Five derivatives were identified as modest inhibitors with 53 to 64% of cN-II inhibition at 1 mM. Keywords

Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

• Svetlana V. Vasilyeva,
• Vyacheslav V. Filichev and
• Alexandre S. Boutorine

Beilstein J. Org. Chem. 2016, 12, 1348–1360, doi:10.3762/bjoc.12.128

• , so they were successfully used for both gene expression regulation and the synthesis of fluorescent probes for DNA imaging in fixed and live cells [1][2][3][8][9]. However, the length of the sequence recognized by the classical hairpin polyamides (5–6 base pairs) is much shorter than that for TFOs

Synthesis of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines

• Eric Buchy,
• Branko Vukosavljevic,
• Maike Windbergs,
• Dunja Sobot,
• Camille Dejean,
• Simona Mura,
• Patrick Couvreur and
• Didier Desmaële

Beilstein J. Org. Chem. 2016, 12, 1127–1135, doi:10.3762/bjoc.12.109

• radioactive labeling 3H,14C has been taken into profit to study the pharmacokinetics, the biodistribution and the metabolism of squalenoyl adenosine nanoparticles [22]. Nevertheless, the synthesis of labeled compounds is chemically challenging, expensive and submitted to drastic regulation rules. In addition

Antibiotics from predatory bacteria

• Juliane Korp,
• María S. Vela Gurovic and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 594–607, doi:10.3762/bjoc.12.58

• biological function of this compound class [63]. Furthermore, the two EBPs were linked to the regulation of the myxovirescin pathway and motility. While HsfA acted as a repressor of the myxovirescin production, MXAN4899 could exert enhancing or inhibitory effects depending on the nutrition status of the

Art, auto-mechanics, and supramolecular chemistry. A merging of hobbies and career

• Eric V. Anslyn

Beilstein J. Org. Chem. 2016, 12, 362–376, doi:10.3762/bjoc.12.40

• wine fraud may be a real-life application for the method. As has Rotello, we are taking our differential sensing work to the biological arena. Kinases are enzymes that are involved in cellular signaling and regulation. Monitoring their activity has commonly involved the creation of highly selective

Natural products from microbes associated with insects

• Christine Beemelmanns,
• Huijuan Guo,
• Maja Rischer and
• Michael Poulsen

Beilstein J. Org. Chem. 2016, 12, 314–327, doi:10.3762/bjoc.12.34

• interaction and regulation mechanisms are likely to be more complex than previously expected. Defensive bacterial symbionts of insects Kaltenpoth and co-workers described one of the most intriguing examples of an insect–bacteria symbiosis and symbiont conferred protection [42][43][44]. Predatory females of

• in vitro analyses, but efforts should be directed towards identifying the presence and activity of candidate compounds in situ. The examination of bacterial secondary metabolisms and the respective small molecules secretome, can give insights into the up or down-regulation of (cryptic) biosynthetic

Simple activation by acid of latent Ru-NHC-based metathesis initiators bearing 8-quinolinolate co-ligands

• Julia Wappel,
• Roland C. Fischer,
• Luigi Cavallo,
• Christian Slugovc and
• Albert Poater

Beilstein J. Org. Chem. 2016, 12, 154–165, doi:10.3762/bjoc.12.17

• nature [1][2], but exploiting similar strategies for synthetic catalysts is still in its infancy [3][4][5]. Prominent examples in catalytic polymerization [6][7] comprise the regulation of molecular weight by allosteric effects [8][9] or influencing the polymers’ microstructure upon changing the monomer

• pressure [10]. Such kind of regulation of the catalysts activity does not only comprise a switching on of a particular feature but also the switching off of this feature upon another (different) stimulus. A simpler but related concept is to turn a latent catalyst [11] or initiator (i.e., ideally a

Synthesis of cyclic N¹-pentylinosine phosphate, a new structurally reduced cADPR analogue with calcium-mobilizing activity on PC12 cells

• Ahmed Mahal,
• Stefano D’Errico,
• Nicola Borbone,
• Brunella Pinto,
• Agnese Secondo,
• Valeria Costantino,
• Valentina Tedeschi,
• Giorgia Oliviero,
• Vincenzo Piccialli and
• Gennaro Piccialli

Beilstein J. Org. Chem. 2015, 11, 2689–2695, doi:10.3762/bjoc.11.289

• synthetic building blocks towards the synthesis of biologically relevant compounds such as antiviral and antineoplastic drugs [3][4][5][6][7][8], antibiotics and antifungal agents [9][10][11]. Furthermore, several NNs act as potent second messengers involved in the regulation of key metabolic pathways [12