Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• and other pathogenicity traits to overwhelm and colonise the host in the infection process [5] and pqs QS plays a crucial role in the regulation of many of those. It is astonishing, that expression of 182 genes is altered in response to exogenous PQS [33]. Evidence has been gathered, that these

• response. In terms of pathogenicity traits, they are involved in the regulation of genes encoding for enzymes responsible for phenazine biosynthesis (pyocyanin production), hydrogen cyanide synthesis, Lectins LecA and LecB and additional genes involved in biofilm formation, enzymes for rhamnolipid

• synthesis, a Resistance-Nodulation-Cell division (RND) efflux pump encoded by mexGHI-opmD operon, components of Type 3 and Type 6 secretion as well as the exotoxin ExoS, and siderophore synthases [33]. In addition to virulence regulation, some remarkable secondary effects have been attributed to the PQS

Impact of Pseudomonas aeruginosa quorum sensing signaling molecules on adhesion and inflammatory markers in endothelial cells

• Carmen Curutiu,
• Florin Iordache,
• Veronica Lazar,
• Aurelia Magdalena Pisoschi,
• Aneta Pop,
• Mariana Carmen Chifiriuc and
• Alina Maria Hoban

Beilstein J. Org. Chem. 2018, 14, 2580–2588, doi:10.3762/bjoc.14.235

• and blood dissemination of the infection [3]. The regulation of the virulence factors expression is coordinated by quorum sensing (QS), an intercellular communication system based on cell density dependent molecules with autoinductory properties that play a pivotal role in the pathogenesis of various

• therapeutic strategies against P. aeruginosa infections, which are very difficult to treat. The vascular endothelium is crucial for cell and tissue homeostasis and regulation of inflammatory response. The loss of its integrity causes plasma, proteins and cells to build up in the interstitial space, resulting

Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty acids

• Eszter Lajkó,
• Sarah Spring,
• Rózsa Hegedüs,
• Beáta Biri-Kovács,
• Sven Ingebrandt,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 2495–2509, doi:10.3762/bjoc.14.226

• the regulation of gonadal steroidogenesis and gametogenesis by integrating the nervous and endocrine system in the pituitary gland [4]. Regarding the targeted chemotherapy, it is highly advantageous that several native GnRH analogs, including the two human isoforms (GnRH-I and GnRH-II), and their

Bioinspired cobalt cubanes with tunable redox potentials for photocatalytic water oxidation and CO₂ reduction

• Zhishan Luo,
• Yidong Hou,
• Jinshui Zhang,
• Sibo Wang and
• Xinchen Wang

Beilstein J. Org. Chem. 2018, 14, 2331–2339, doi:10.3762/bjoc.14.208

• reactions. The “Co4O4” cubane complex Co4O4(CO2Me)4(RNC5H4)4 (R = CN, Br, H, Me, OMe), serves as a molecular catalyst for the efficient and stable photocatalytic water oxidation and CO2 reduction. A comprehensive structure–function analysis emerged herein, highlights the regulation of electronic

• redox potentials reflect a dependence on the electronic properties of the ligand. This again underlines, that the ligands are playing a significant role in the regulation of the redox properties of the 1-R complexes. To further estimate the impact of ligand substitution, the complexes were analyzed by

Rational design of boron-dipyrromethene (BODIPY) reporter dyes for cucurbit[7]uril

• Mohammad A. Alnajjar,
• Jürgen Bartelmeß,
• Robert Hein,
• Pichandi Ashokkumar,
• Mohamed Nilam,
• Werner M. Nau,
• Knut Rurack and
• Andreas Hennig

Beilstein J. Org. Chem. 2018, 14, 1961–1971, doi:10.3762/bjoc.14.171

• combination of properties has enabled numerous applications in the life sciences, for example, for protein binding [5][6], stabilization [7], immobilisation [8], isolation [9], self-assembly [10][11], and regulation [12], or for drug solubilisation and delivery [13][14][15]. The combination of CBs with

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

• structural analogs of distamycin, netropsin and thiazotropsins were developed to test their DNA binding affinity, sequence specificity and cytotoxicity, thereby eventually developing a general approach for the regulation of gene expression by DNA binding small molecules. However, all these analogs do not

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• individually incorporated into the polymersomes and mixed together in solution; in both of the cases the final product formation was monitored by UV–vis spectroscopy. The control over the pH allowed the regulation of the enzymatic cascade (no product was observed at pH 8 in both of the reactive systems), as

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

• in vitro as in HeLa cells. Modifications at the nucleobase For selected reviews on this topic, see [79][80]. From all possible photoresponsive modifications introduced into ONs, modifications of the nucleobases are the most widely used for the regulation of gene expression under light activation. For

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• ). Application of natural or synthetic TLR4 antagonists represents one of the most effective approaches for down-regulation of the TLR4-mediated signaling. So far, several lipid A variants which can block the LPS-binding site on human (h)MD-2 have been identified: tetraacylated lipid IVa [47] and a non

• -pathogenic lipid A from R. sphaeroides [22][48], which served as structural basis for the synthetic antisepsis drug candidate eritoran [49][50]. Inadequate regulation of the TLR4-mediated signaling was recognized as crucial factor in the pathogenesis of chronic inflammatory, autoimmune and infectious

• diseases [51][52][53]. A number of studies also suggested a possible implication of TLR4 in cardiovascular disorders [54] and Alzheimer desease – associated pathology [55]. Therapeutic down-regulation of the TLR4 signaling is believed to be beneficial for treatment of numerous chronic and acute

A concise flow synthesis of indole-3-carboxylic ester and its derivatisation to an auxin mimic

• Marcus Baumann,
• Ian R. Baxendale and
• Fabien Deplante

Beilstein J. Org. Chem. 2017, 13, 2549–2560, doi:10.3762/bjoc.13.251

• , this created a convenient staging point to generate intermediate holding batches of material for subsequent on demand processing. Overall we envisage this laboratory scale design to offer several opportunities for further development enabling quick up regulation of production in the future

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