Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• peptide from prealbumin. This means that macrolactam formation is somewhat inefficient and a significant amount of acyclic SFTI-1 is also produced, but this is masked by the rapid in vivo degradation of this unwanted side-product [105]. Gene silencing experiments have linked AEP-like proteins to the

• cysteine protease-like mechanism [118]. In vivo, this staphylococcal protein ligates proteins with a C-terminal LPXTG motif to the peptidoglycan, via the formation of an enzyme bound thioester on the threonine residue, and has been used widely as an enzymatic tool for ligation to proteins with an LPXTG tag

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

• , the use of fluorescent probes requires the covalent binding of large dye molecules (bodipy, cyanine, rhodamine etc, ...) to the drug conjugate, thus potentially modifying its physicochemical profile as well as the in vivo fate and the pharmacological activity. A simple encapsulation of an amphiphilic

• , have been developed to study the stability of nanoparticles [23]. In this context, Raman spectroscopy is an interesting technique which is based on the detection of scattered laser light upon irradiating the sample. Nevertheless, because of the low intensity of the Raman scattering, efficient in vivo

Efficient syntheses of climate relevant isoprene nitrates and (1R,5S)-(−)-myrtenol nitrate

• Sean P. Bew,
• Glyn D. Hiatt-Gipson,
• Graham P. Mills and
• Claire E. Reeves

Beilstein J. Org. Chem. 2016, 12, 1081–1095, doi:10.3762/bjoc.12.103

• sector in generating structure and function diverse O-nitrate esters for use as in vivo NO-donors. In this context particular emphasis has been placed on developing O-nitrate esters as biologically active agents that act on acetylcholinesterase (AChE), amyloid-βx-42 (Aβ42) aggregation, cyclooxygenase-II

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• agents is of growing significance. The discovery of penicillin [1] and the proof of its in vivo efficacy [2] marked the starting point for the research on antibacterial drugs during the so-called "golden age" of antibiotics. Despite the early occurrence of first resistances [3][4][5], an innovation gap

• with MIC values of 2 to 16 μg/mL, Enterococci with 16 μg/mL and higher to some Gram-negative bacteria (8 μg/mL). Against an E. coli mutant with increased membrane permeability, an MIC value below 0.03 μg/mL was obtained, suggesting that inhibition is a matter of cellular uptake of the compound. In vivo

Three new trixane glycosides obtained from the leaves of Jungia sellowii Less. using centrifugal partition chromatography

• Luíse Azevedo,
• Larissa Faqueti,
• Marina Kritsanida,
• Antonia Efstathiou,
• Despina Smirlis,
• Gilberto C. Franchi Jr,
• Grégory Genta-Jouve,
• Sylvie Michel,
• Louis P. Sandjo,
• Raphaël Grougnet and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2016, 12, 674–683, doi:10.3762/bjoc.12.68

• -inflammatory and antioxidant effects of J. paniculata were associated to the presence of flavonoids and other polyphenols [4]. Recently, we reported the in vivo anti-inflammatory properties of an aqueous fraction of the leaves of J. sellowii, that is in agreement with its popular use in Brazil [5]. Apart from

Unconventional application of the Mitsunobu reaction: Selective flavonolignan dehydration yielding hydnocarpins

• Guozheng Huang,
• Simon Schramm,
• Jörg Heilmann,
• David Biedermann,
• Vladimír Křen and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 662–669, doi:10.3762/bjoc.12.66

• hepatotoxicity in vitro as well as in vivo [10][11]. The flavonolignan hydnocarpin (4, Figure 1) was first isolated in 1973 from Hydnocarpus wightiana [12], and its structure was at first assigned erroneously as what is now named hydnocarpin D (2, Figure 1) (for details see below) [13]. The actual hydnocarpin D

• towards chemotherapy and no toxicity was found in vivo [20]. Unlike for silybins [6], there are only a few examples of total syntheses or even structural modifications of hydnocarpin-type (flavone) flavonolignans – simply because they are not synthetically available [14][21]. A straightforward synthetic

A practical way to synthesize chiral fluoro-containing polyhydro-2H-chromenes from monoterpenoids

• Oksana S. Mikhalchenko,
• Dina V. Korchagina,
• Konstantin P. Volcho and
• Nariman F. Salakhutdinov

Beilstein J. Org. Chem. 2016, 12, 648–653, doi:10.3762/bjoc.12.64

• the presence of K10 montmorillonite clay forms chiral heterocyclic compounds with the hexahydro-2H-chromene scaffold 2 (Scheme 1) [1][2][3][4]. Products of these reactions are of interest as many of them exhibit a significant analgesic activity in vivo [2][3][4]. In terms of structure–activity

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• ’-dichlorodihydrofluorescein (DCFH) to the fluorescent 2’,7’-dichlorofluorescein (DCF) [29]. This antioxidant activity was also linked to anti-inflammatory effects by testing the in vivo effects of 23 in a carrageenan-induced paw edema assay. Oral administration of 23 to mice prior to carrageenan injection resulted in a

• A was also tested successfully using an in vivo mouse model for the treatment of infections with filarial nematodes [44]. Such antibiotics produced by heterotroph bacteria, e.g., marine and terrestrial myxobacteria which can feed on other bacteria, are suggested as predatory weapons to paralyze and

• interesting target of research, due to the fact that the progression of Alzheimer’s disease was slowed down by using anti-inflammatory drugs. Thus, selective COX-2 inhibitors, anti-inflammatory compounds themselves, might have beneficial effects in vivo. Several derivatives of 6-alkyl (alkoxy or alkylthio)-4

Effective in silico prediction of new oxazolidinone antibiotics: force field simulations of the antibiotic–ribosome complex supervised by experiment and electronic structure methods

• Jörg Grunenberg and
• Giuseppe Licari

Beilstein J. Org. Chem. 2016, 12, 415–428, doi:10.3762/bjoc.12.45

• potency both in vitro and in vivo antibacterial activities [46]. Candidate 7 represents the active form of the prodrug torezolid, the phosphate disodium salt, which was synthetized in order to improve the solubility of its parent drug. Highly active against MRSA, MSSA (methicillin-sensitive Staphylococcus

Diastereoselective synthesis of new O-alkylated and C-branched inositols and their corresponding fluoro analogues

• Charlotte Collet,
• Françoise Chrétien,
• Yves Chapleur and
• Sandrine Lamandé-Langle

Beilstein J. Org. Chem. 2016, 12, 353–361, doi:10.3762/bjoc.12.39

• the corresponding fluoroinositol (1-fluoro-1-deoxy-scyllo-inositol) was also a good candidate to limit this aggregation. However, in vivo studies in animal models of Alzheimer disease with 1-[18F]fluoro-1-deoxy-scyllo-inositol used as radiotracer for positron emission tomography (PET) have shown that

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

• , in vivo infection studies coupled with methods such as RNA sequencing, can lead to further insights into the role and expression levels of potentially new secondary metabolites. Conclusion Insects provide experimentally tractable and cost-effective model systems to investigate the evolutionary

• (e.g., bafilomycin A1 (21) and B1 (22), Figure 7), but also a novel polyunsaturated and polyoxygenated 26-membered macrolactam named sceliphrolactam (23) (Figure 7) [101]. Sceliphrolactam showed strong antifungal activity against amphotericin B-resistant Candida albicans, but its functional role in

• vivo remains enigmatic. In another study, Oh and co-workers chemically investigated a diverse population of Actinobacteria from the indigenous soil-dwelling Korean dung beetle (Copris tripartitus), its larvae and dung balls [102][103]. Dung beetles are prime contributors to the cyclic breakdown of

A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

• Steven C. Zimmerman

Beilstein J. Org. Chem. 2016, 12, 125–138, doi:10.3762/bjoc.12.14

• in vivo using a DM1 Drosophila model that looked at the rough eye phenotype with i(CUG)480 flies. Ligand 30 showed significant and dose-dependent improvement in the rough eye phenotype, whereas the negative control, DB213 showed much weaker activity. Much less effort has been devoted to developing

• CUGexp, also binding CUGexp that slips through inhibiting its sequestration of MBNL1, and, with the catalytic amino/ammonium/imidazole groups, slowly cleaving the CUG-RNA to prevent RAN translation [92]. Edwin Chan and his group again studied the in vivo activity of our compounds, showing that 32

Bright molecules for sensing, computing and imaging: a tale of two once-troubled cities

• A. Prasanna de Silva

Beilstein J. Org. Chem. 2015, 11, 2774–2784, doi:10.3762/bjoc.11.298

• assiduously. In other words, some of these Colombo residents (like I was) are now alive thanks to a fluorescent PET sensor. In addition to this ex vivo application, which had an easier accreditation process through the medical watchdog institutions as compared to an in vivo version, there are emerging

Assembly of synthetic Aβ miniamyloids on polyol templates

• Sebastian Nils Fischer and
• Armin Geyer

Beilstein J. Org. Chem. 2015, 11, 2646–2653, doi:10.3762/bjoc.11.284

• formation [2]. Alternatively, it is started by seeding with amyloid fragments whose large surface-to-core ratio greatly accelerates the fibril formation. Although amyloid structures are well studied in vitro, their in vivo relevance at the onset of Alzheimer’s disease remains under debate [3]. Aβ peptides

Inclusion complexes of 2-methoxyestradiol with dimethylated and permethylated β-cyclodextrins: models for cyclodextrin–steroid interaction

• Mino R. Caira,
• Susan A. Bourne,
• Halima Samsodien and
• Vincent J. Smith

Beilstein J. Org. Chem. 2015, 11, 2616–2630, doi:10.3762/bjoc.11.281

• literature. Encapsulation of poorly soluble drug molecules by CDs with the aim of enhancing drug bioavailability has been practised for over four decades, the first demonstration of both in vivo and in vitro effects of complexation on drug release having been reported in the early 1970s [12][13]. Steroid

Smart molecules for imaging, sensing and health (SMITH)

• Bradley D. Smith

Beilstein J. Org. Chem. 2015, 11, 2540–2548, doi:10.3762/bjoc.11.274

• microscopy and flow cytometry methods for preclinical research [13][14][15][16] (Figure 2). Many of these fluorescent probes are used as imaging reagents to quantify the level of cell death in a range of biomedical samples [17]. We also developed some nuclear isotopic labeled probes for in vivo imaging of

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• mevalonate/deoxyxylulose-level for in vivo feeding experiments or oligoprenyl diphosphates for in vitro studies to understand the often complex cyclization cascades catalyzed by a single enzyme. In many cases, isotopes represent the only way of elucidating proposed hydride shifts, carbon–carbon

• melanosporofaciens [64]. The cyclization of geranylgeranyl diphosphate (GGPP, 44) to 52 features an unexpected carbon backbone rearrangement, which was shown recently by Kuzuyama and co-workers using isotopically labeled glucose in vivo and labeled GGPP in vitro [65]. The reaction is catalysed by the enzyme CotB2

• combined in vivo and in vitro labeling techniques to achieve a better understanding of nature’s astonishing mechanistic toolbox utilized by terpene synthases. Additionally, the unexpected outcome of the initial feeding experiment gives an ideal example as to why isotopic labeling experiments are not at all

Easy access to heterobimetallic complexes for medical imaging applications via microwave-enhanced cycloaddition

• Nicolas Desbois,
• Sandrine Pacquelet,
• Adrien Dubois,
• Clément Michelin and
• Claude P. Gros

Beilstein J. Org. Chem. 2015, 11, 2202–2208, doi:10.3762/bjoc.11.239

• chloride, chloroform or methanol [12] thus MRI applications of Gd-porphyrins are difficult to envisage. Manganese. The design of gadolinium complex did not fully eliminate the risk of in vivo release and accumulation which is a common problem implicated in nephrogenic systemic fibrosis. A possible solution

• [16][17] and porphyrins as PET probes. Cu–NOTA is significantly more inert in acidic conditions compared to Cu–DOTA, which usually decomplexed within few minutes. 64Cu2+-NOTA is considered as better PET agent, with regard to its in vivo stability [18]. Porphyrins are also excellent macrocyclic ligands

• applications [24]. Indium-111. One major isotope used within DOTA–SPECT agents is 111In (displaying a half-live of 67 hours). It should be noted that the well-established 111In–DOTA is in vivo robust [25] and many articles have been reported in the literature highly supporting the potential convenient utility

Cholesterol lowering effects of mono-lactose-appended β-cyclodextrin in Niemann–Pick type C disease-like HepG2 cells

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

Beilstein J. Org. Chem. 2015, 11, 2079–2086, doi:10.3762/bjoc.11.224

• exert the pharmacological effects in vivo, since neither HP-β-CyD nor HP-γ-CyD enters cells effectively due to their hydrophilicity and high molecular weight. Receptor-mediated endocytosis is an attractive approach to enhance the cellular uptake of drugs in target cells. It enables not only high drug

Effective ascorbate-free and photolatent click reactions in water using a photoreducible copper(II)-ethylenediamine precatalyst

• Redouane Beniazza,
• Natalia Bayo,
• Florian Molton,
• Carole Duboc,
• Stéphane Massip,
• Nathan McClenaghan,
• Dominique Lastécouères and
• Jean-Marc Vincent

Beilstein J. Org. Chem. 2015, 11, 1950–1959, doi:10.3762/bjoc.11.211

• copper salts, which should be avoided for in vivo applications and, when employed, by sodium ascorbate and/or its byproducts; (iii) side-reactions on the substrates due to the generation of reduced dioxygen-active species and/or reactive oxidized byproducts of ascorbate. In a seminal paper, Finn and

Dicarboxylic esters: Useful tools for the biocatalyzed synthesis of hybrid compounds and polymers

• Ivan Bassanini,
• Karl Hult and
• Sergio Riva

Beilstein J. Org. Chem. 2015, 11, 1583–1595, doi:10.3762/bjoc.11.174

• disulfide exchange reactions in vivo [42][43]. All of these compounds were synthesized by (sometimes troublesome) chemical protocols requiring accurate control of the reaction conditions and several protection/deprotection steps. This is avoided using a biocatalyzed approach, as it has been shown exploiting

Synthesis and evaluation of the biostability and cell compatibility of novel conjugates of nucleobase, peptidic epitope, and saccharide

• Dan Yuan,
• Xuewen Du,
• Junfeng Shi,
• Ning Zhou,
• Abdulgader Ahmed Baoum,
• Khalid Omar Al Footy,
• Khadija Omar Badahdah and
• Bing Xu

Beilstein J. Org. Chem. 2015, 11, 1352–1359, doi:10.3762/bjoc.11.145

• ). Biostability The existence of proteolytic enzymes [39] in organism limits the applications of peptide-based biomaterials [40] in vivo. To evaluate the biostability of the conjugates 1–8, we incubated them with proteinase K (a powerful protease) in HEPES buffer at 37 °C for 24 h. As shown in Figure 3A

• stable hydrogel, which increases the biostability of 8. Meanwhile, 5, 8, and their mixture show excellent cell compatibility, which is a basic requirement for multi-application in vivo (e.g., wound healing [45]). This work provides a new approach to develop biocompatible soft materials. Experimental

Terminal lipophilization of a unique DNA dodecamer by various nucleolipid headgroups: Their incorporation into artificial lipid bilayers and hydrodynamic properties

• Emma Werz and
• Helmut Rosemeyer

Beilstein J. Org. Chem. 2015, 11, 913–929, doi:10.3762/bjoc.11.103

• complex nanoarchitectures [33][34], the interaction of such nanostructures with lipid membranes [35][36][37][38], as well as the optimization of the in vivo delivery of lipophilic siRNA [10][11][12] (e.g., by DNA trafficking [7]). Further studies from our group will include the binding of terminally

N-Alkyl derivatives of diosgenyl 2-amino-2-deoxy-β-D-glucopyranoside; synthesis and antimicrobial activity

• Agata Walczewska,
• Daria Grzywacz,
• Dorota Bednarczyk,
• Małgorzata Dawgul,
• Andrzej Nowacki,
• Wojciech Kamysz,
• Beata Liberek and
• Henryk Myszka

Beilstein J. Org. Chem. 2015, 11, 869–874, doi:10.3762/bjoc.11.97

• Standards Institute (CLSI) for 8–15 and 17 as well as for 7 hydrochloride are summarized in Table 2 and Table 3. The latter was added as the reference since its high in vitro activities and in vivo efficacy were proved [53]. The determined MIC values indicate that compounds explored have rather poor if any

Multivalent dendritic polyglycerolamine with arginine and histidine end groups for efficient siRNA transfection

• Fatemeh Sheikhi Mehrabadi,
• Hanxiang Zeng,
• Mark Johnson,
• Cathleen Schlesener,
• Zhibin Guan and
• Rainer Haag

Beilstein J. Org. Chem. 2015, 11, 763–772, doi:10.3762/bjoc.11.86

• more are being developed [1]. Although a direct delivery of “naked” siRNA or chemically modified oligonucleotides [2] has been studied, delivery vectors are typically required for efficient siRNA delivery in vivo due to unmodified siRNA’s low stability towards endogenous enzymes, poor cellular uptake

• and degrees of branching [5]. Additionally, dPG has multiple groups for further functionalization, high chemical stability, and good biocompatibility in vitro and in vivo [6][7][8]. All these characteristics make dPG an ideal scaffold for a broad range of applications from anti fouling [9] to

• potential of dPG-NH2 with high amine loading (≥90%) for siRNA delivery in vivo [22]. Moreover, it has been shown that dPG-NH2 90% is able to efficiently downregulate the formation of several proteins in vitro [23]. In spite of its high efficiency, the therapeutic window of dPG-NH2 90% is small and the