SF002-96-1, a new drimane sesquiterpene lactone from an Aspergillus species, inhibits survivin expression

• Silke Felix,
• Louis P. Sandjo,
• Till Opatz and
• Gerhard Erkel

Beilstein J. Org. Chem. 2013, 9, 2866–2876, doi:10.3762/bjoc.9.323

• of apoptosis, regulation of cell proliferation, metastasis and resistance to therapy. Because of its upregulation in malignancy, survivin has currently attracting considerable interest as a new target for anticancer therapy. In a screening of approximately 200 strains of imperfect fungi for the

• with an IC50 value of 2.63 µM (1 µg/mL). Previous studies in colon cancer cells have shown that regulation of survivin expression is, in addition, TCF/β-catenin dependent mediated by three TCF/β-catenin consensus sequences within the survivin promoter [20]. Dysregulation of TCF/β-catenin dependent gene

• regulation originating from aberrantly stabilized β-catenin or mutations in the associated protein adenomatous polyposis coli (APC) results in the activation of target genes implicated in cell proliferation and transformation [21]. We therefore investigated the effect of SF002-96-1 on canonical Wnt signaling

The regulation and biosynthesis of antimycins

• Ryan F. Seipke and
• Matthew I. Hutchings

Beilstein J. Org. Chem. 2013, 9, 2556–2563, doi:10.3762/bjoc.9.290

• over-produced in cancer cells that are resistant to apoptosis-inducing chemotherapy agents, so antimycins have great potential as anticancer drugs used in combination with existing chemotherapeutics. Here we review what is known about antimycins, the regulation of the ant gene cluster and the unusual

• biosynthetic pathway. Keywords: antimycins; gene regulation; genome mining; natural products; Streptomyces; Review It is estimated that around 60% of all known antibiotics are derived from secondary metabolites made by filamentous actinomycete bacteria, most notably Streptomyces species [1]. Streptomyces

• interest in better understanding the biosynthesis and regulation of antimycins, with a view toward bioengineering improved pharmacological properties for the treatment of drug-resistant cancers in the future. The ant gene cluster Since our discovery of the ant gene cluster in S. albus S4, we and others

Synthesis of the calcilytic ligand NPS 2143

• Henrik Johansson,
• Thomas Cailly,
• Alex Rojas Bie Thomsen,
• Hans Bräuner-Osborne and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2013, 9, 1383–1387, doi:10.3762/bjoc.9.154

• modulator on the CaSR (1, Figure 1) [5]. The CaSR is the main regulator of serum calcium homeostasis and plays a central role in several cellular processes such as secretion and regulation of peptide hormones (most importantly parathyroid hormone), ion-channel activity and apoptosis in certain cell types [6

• ][7][8]. The CaSR is involved in several calcium-regulation-related diseases including various types of hypo- and hyperparathyroidism, and its pronounced regulation of parathyroid hormone secretion makes it an interesting target for drug discovery [9]. Several potent CaSR modulators have been reported

Synthesis and physicochemical characterization of novel phenotypic probes targeting the nuclear factor-kappa B signaling pathway

• Paul M. Hershberger,
• Satyamaheshwar Peddibhotla,
• E. Hampton Sessions,
• Daniela B. Divlianska,
• Ricardo G. Correa,
• Anthony B. Pinkerton,
• John C. Reed and
• Gregory P. Roth

Beilstein J. Org. Chem. 2013, 9, 900–907, doi:10.3762/bjoc.9.103

• ), Raf (57%), and JAK2 (53%)) are relevant to NF-κB pathway regulation. To prepare 4, a synthetic route (Scheme 1) was optimized in a manner that allowed for the preparation of related analogues [9]. The intermediate 1 was prepared through condensation of 4,5-dimethylbenzene-1,2-diamine with potassium

Recent progress in the discovery of small molecules for the treatment of amyotrophic lateral sclerosis (ALS)

• Allison S. Limpert,
• Margrith E. Mattmann and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2013, 9, 717–732, doi:10.3762/bjoc.9.82

• activation of DAO or reduction of serine racemase (SR), the enzyme responsible for D-serine synthesis, may be therapeutically beneficial [20]. Furthermore, drugs modulating NMDA receptor signaling may also prove beneficial to ALS treatment. The contribution of improper glutamate regulation to ALS pathology

• neuroprotection is to inhibit the signaling molecules that antagonize cellular survival and promote neuron death in disease models. Glycogen synthase kinase-3 (GSK-3) is an essential signaling molecule involved in many cellular processes including glycogen metabolism, cell-cycle regulation, cellular proliferation

Thioester derivatives of the natural product psammaplin A as potent histone deacetylase inhibitors

• Matthias G. J. Baud,
• Thomas Leiser,
• Vanessa Petrucci,
• Mekala Gunaratnam,
• Stephen Neidle,
• Franz-Josef Meyer-Almes and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2013, 9, 81–88, doi:10.3762/bjoc.9.11

• . Keywords: epigenetics; histone deacetylase; natural product; prodrug; psammaplin A; thioester; Introduction Chromatin is a macromolecular complex consisting of DNA, histone and nonhistone proteins. The epigenetic control of chromatin organization plays a major role in the regulation of gene expression

Asymmetric synthesis of γ-chloro-α,β-diamino- and β,γ-aziridino-α-aminoacylpyrrolidines and -piperidines via stereoselective Mannich-type additions of N-(diphenylmethylene)glycinamides across α-chloro-N-sulfinylimines

• Gert Callebaut,
• Sven Mangelinckx,
• Pieter Van der Veken,
• Karl W. Törnroos,
• Koen Augustyns and
• Norbert De Kimpe

Beilstein J. Org. Chem. 2012, 8, 2124–2131, doi:10.3762/bjoc.8.239

• specifically cleave off N-terminal dipeptides and are involved in the degradation of incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). GLP-1 is involved in the regulation of glucose homeostasis through stimulation of insulin secretion

Restructuring polymers via nanoconfinement and subsequent release

• Alan E. Tonelli

Beilstein J. Org. Chem. 2012, 8, 1318–1332, doi:10.3762/bjoc.8.151

• preferentially degraded by the enzyme. Regulation of their biodegradation behavior, through formation of and coalescence from CD ICs, may enhance the use of block copolymers in drug delivery and controlled release systems, because of its decisive importance in these applications. Coalesced polymer blends

Control over molecular motion using the cis–trans photoisomerization of the azo group

• Estíbaliz Merino and
• María Ribagorda

Beilstein J. Org. Chem. 2012, 8, 1071–1090, doi:10.3762/bjoc.8.119

• illumination, by means of the direct regulation of enzymatic activity [64][65][66][67], peptides, proteins, nucleic acids [68][69][70][71][72][73][74][75][76], receptors [77][78][79][80][81][82], or ion channels [83][84][85], or by modulation of the concentration of several labelled molecules. This strategy is

Chemo-enzymatic modification of poly-N-acetyllactosamine (LacNAc) oligomers and N,N-diacetyllactosamine (LacDiNAc) based on galactose oxidase treatment

• Christiane E. Kupper,
• Ruben R. Rosencrantz,
• Birgit Henßen,
• Helena Pelantová,
• Stephan Thönes,
• Anna Drozdová,
• Vladimir Křen and
• Lothar Elling

Beilstein J. Org. Chem. 2012, 8, 712–725, doi:10.3762/bjoc.8.80

• regulation [62][63]. Binding analysis of different galectins to these novel poly-LacNAc derivatives is currently under investigation. The production of poly-LacNAc chains with one or more modified galactose residues will allow further insight in detailed protein-glycan binding mechanisms. In the past mainly

Mutational analysis of a phenazine biosynthetic gene cluster in Streptomyces anulatus 9663

• Orwah Saleh,
• Katrin Flinspach,
• Lucia Westrich,
• Andreas Kulik,
• Bertolt Gust,
• Hans-Peter Fiedler and
• Lutz Heide

Beilstein J. Org. Chem. 2012, 8, 501–513, doi:10.3762/bjoc.8.57

• identified in nearly all investigated bacterial strains that produce phenazine compounds [3][6]. Other genes have been shown to play a role in the regulation of phenazine biosynthesis. In P. fluorescens, the transcriptional regulation involves the quorum sensing proteins PhzR/PhzI, the positive two-component

• regulation of the biosynthesis of phenazine natural products. In a previous study, we described the biosynthetic gene cluster for prenylated phenazines from Streptomyces anulatus (Figure 1) [11]. This cluster contained the seven core phenazine biosynthesis genes, the mevalonate pathway genes and a

• individual genes of this cluster for the biosynthetic pathway and for its regulation. The genes inactivated in this study are summarized in Table 1, and a complete list of the genes contained in the insert of cosmid ppzOS04 is given in Table S1 of Supporting Information File 1. Results and Discussion

Conserved and species-specific oxylipin pathways in the wound-activated chemical defense of the noninvasive red alga Gracilaria chilensis and the invasive Gracilaria vermiculophylla

• Martin Rempt,
• Florian Weinberger,
• Katharina Grosser and
• Georg Pohnert

Beilstein J. Org. Chem. 2012, 8, 283–289, doi:10.3762/bjoc.8.30

• potential of Gracilaria spp. is discussed. Keywords: activated chemical defense; invasive species; oxylipins; prostaglandins; red algae; regulation; Introduction The red alga Gracilaria chilensis is native along the Chilean coast and is commercially farmed for the production of agar hydrocolloids [1

• chemical defense against epiphytism has been demonstrated. This alga has two major lines of defense, including a rapid wound-activated production of oxylipins and a slower induced defense involving the up regulation of phospholipases and lipoxygenases and subsequent fatty-acid transformation [3][5]. Among

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

A bivalent glycopeptide to target two putative carbohydrate binding sites on FimH

• Thisbe K. Lindhorst,
• Kathrin Bruegge,
• Andreas Fuchs and
• Oliver Sperling

Beilstein J. Org. Chem. 2010, 6, 801–809, doi:10.3762/bjoc.6.90

• light of very recent findings, our observations as well as results with other multivalent ligands, might be well explained by an allosteric model of FimH-mediated adhesion [35]. It has been reported that interdomain allosteric regulation can lead to a catch bond mechanism of adhesion in which the

• regulation of the ligand-receptor interaction. Experimental Docking studies Computer-aided modeling to estimate the spacer lengths of a bivalent glycopeptide ligand to allow bridging of two putative binding sites on FimH was carried out using FlexX flexible docking and consensus scoring, implemented in Sybyl

Bioorthogonal metabolic glycoengineering of human larynx carcinoma (HEp-2) cells targeting sialic acid

• Arne Homann,
• Riaz-ul Qamar,
• Sevnur Serim,
• Petra Dersch and
• Jürgen Seibel

Beilstein J. Org. Chem. 2010, 6, No. 24, doi:10.3762/bjoc.6.24

• effects is known [11]. Recently, the regulation of UDP-GlcNAc 2-epimerase/ManNAc kinase expression on the transcriptional level by DNA methylation was demonstrated [12] and a genetic feedback regulation for this process was proposed (Scheme 3) [13]. Ac4GlcNAz 16 or Neu5Hex 3, respectively, were incubated

The first preparative solution phase synthesis of melanotan II

• Vladimir V. Ryakhovsky,
• Georgy A. Khachiyan,
• Nina F. Kosovova,
• Elena F. Isamiddinova and
• Andrey S. Ivanov

Beilstein J. Org. Chem. 2008, 4, No. 39, doi:10.3762/bjoc.4.39

• formula Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2 (1), involved in the regulation of skin pigmentation. Production of this hormone is stimulated by irradiation of skin by the sun’s ultraviolet rays. The α-MSH triggers the skin tanning, a process in which skin tanning cells (melanocytes

Do α-acyloxy and α-alkoxycarbonyloxy radicals fragment to form acyl and alkoxycarbonyl radicals?

• Dennis P. Curran and
• Tiffany R. Turner

Beilstein J. Org. Chem. 2006, 2, No. 10, doi:10.1186/1860-5397-2-10

• coupled regulation of radical generation and removal. Among the non-chain methods, generation and removal of radicals by oxidation and reduction are important, as is the "persistent radical effect" [4]. Recently, Wille and coworkers have described a collection of innovative new transformations that they