Development of a fluorogenic small substrate for dipeptidyl peptidase-4

• Futa Ogawa,
• Masanori Takeda,
• Kanae Miyanaga,
• Keita Tani,
• Ryuji Yamazawa,
• Kiyoshi Ito,
• Atsushi Tarui,
• Kazuyuki Sato and
• Masaaki Omote

Beilstein J. Org. Chem. 2017, 13, 2690–2697, doi:10.3762/bjoc.13.267

• sometimes inconvenient in terms of membrane permeability, water solubility, and inhibition of inherent interactions between the probe molecule and the target enzyme. We have developed a new OFF–ON probe with a small fluorescent core unit. The same approach was recently used to produce a fluorophore for a

Membrane properties of hydroxycholesterols related to the brain cholesterol metabolism

• Malte Hilsch,
• Ivan Haralampiev,
• Peter Müller,
• Daniel Huster and
• Holger A. Scheidt

Beilstein J. Org. Chem. 2017, 13, 720–727, doi:10.3762/bjoc.13.71

• of several hydroxycholesterols with those of cholesterol using 2H NMR spectroscopy, a membrane permeability assay, and fluorescence microscopy experiments. It is shown that hydroxycholesterols do not exert the unique impact on membrane properties characteristic for cholesterol with regard to the

• influence on lipid chain order, membrane permeability and formation of lateral domains. Keywords: cholesterol; fluorescence; hydroxycholesterol; membrane structure; NMR; Introduction Cholesterol is a major component of mammalian cell membranes with various biological functions. It plays a key role in

• properties such as lipid chain packing, membrane permeability, and membrane domain formation is investigated. These parameters are compared with those obtained for cholesterol by using various biophysical techniques such as NMR and fluorescence spectroscopy as well as fluorescence microscopy. Results Lipid

Synthesis of acylhydrazino-peptomers, a new class of peptidomimetics, by consecutive Ugi and hydrazino-Ugi reactions

• Angélica de Fátima S. Barreto,
• Veronica Alves dos Santos and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2016, 12, 2865–2872, doi:10.3762/bjoc.12.285

• peptoids the side chain of the Cα is bound to the nitrogen atom. Due to the consequent lack of the polar N–H bonds, their lipophilicity is increased, which may result in improved membrane permeability [16][17]. Furthermore, peptoids have also found utility in supra- and macromolecular engineering [18] and

Computational methods in drug discovery

• Sumudu P. Leelananda and
• Steffen Lindert

Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

• membrane proteins where membrane permeability is considered to be important for drugs to be useful [10][11]. Successes have been reported for SBDD and it has contributed to many compounds reaching clinical trials and get FDA approvals to go into the market [12]. HIV-1 (Human Immunodeficiency Virus I

Biomimetic synthesis and HPLC–ECD analysis of the isomers of dracocephins A and B

• Viktor Ilkei,
• András Spaits,
• Anita Prechl,
• Áron Szigetvári,
• Zoltán Béni,
• Miklós Dékány,
• Csaba Szántay Jr,
• Judit Müller,
• Árpád Könczöl,
• Ádám Szappanos,
• Attila Mándi,
• Sándor Antus,
• Ana Martins,
• Attila Hunyadi,
• György Tibor Balogh,
• György Kalaus (†),
• Hedvig Bölcskei,
• László Hazai and
• Tibor Kurtán

Beilstein J. Org. Chem. 2016, 12, 2523–2534, doi:10.3762/bjoc.12.247

• lowest acidic pKa values are predominant in physiological environment, which is also indicated by the difference of log D values between pH 7.4 and pH 6.5. The blood–brain barrier (BBB) specific penetration of dracocephins isomers has also been studied by the PAMPA (parallel artificial membrane

• permeability assay)-BBB model system, which indicates passive diffusion of test compounds across the brain capillary endothelium. Although naringenin ((±)-1) showed a medium penetration characteristic in this model system, dracocephins A (2a–d) and B (3a–d) had been described as poorly and practically non

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• therapeutical candidates because of their high lipophilicity and membrane permeability [44][51]. A major catalytic entry to α,α-disubstituted (quaternary) amino acids is the α-functionalization of an appropriate template as, for instance, an α-imino ester or lactone, followed by hydrolysis [49][52][53]; but

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

• , Enterococcus MIC: 16–64 µg/mL) but also a few Gram-negative bacteria (E. coli MIC: down to 0.03 μg/mL). Since the activity against wild-type E. coli is clearly lower (MIC > 128 μg/mL) [22], it is assumed that this might be an effect resulting from low membrane permeability. There are other naturally occurring

• 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

Electrochemical oxidation of cholesterol

• Jacek W. Morzycki and
• Andrzej Sobkowiak

Beilstein J. Org. Chem. 2015, 11, 392–402, doi:10.3762/bjoc.11.45

• affords different products depending on the reaction conditions. Keywords: allylic oxidation; cholesterol; electrochemical halogenation; electrochemical oxidation; Introduction Cholesterol is the most common steroid in the mammalian body. It is necessary to ensure a proper membrane permeability and

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

• to 5, thereby mitigating the high calculated log P to some degree. Probes 8 and 12 also showed good solubility. Probe 13 had moderate solubility, and 17 showed the lowest solubility across the pH range but still approximately equal to its IC50 value. The PAMPA (parallel artificial membrane

• permeability assay) assay is used as an in vitro model of passive, transcellular permeability. An artificial membrane immobilized on a filter is placed between a donor and acceptor compartment. In this test, the probes exhibited good cell permeability overall. Although metabolic stability was poor in the

Chemical modification allows phallotoxins and amatoxins to be used as tools in cell biology

• Jan Anderl,
• Hartmut Echner and
• Heinz Faulstich

Beilstein J. Org. Chem. 2012, 8, 2072–2084, doi:10.3762/bjoc.8.233

• parameter was important, since cytotoxicity depends not only on membrane permeability but also on actin affinity. Moreover, this parameter will hint on whether phalloidin was cleaved from its carrier inside the cell, in cases where low actin affinity of a phalloidin derivative was combined with high

• protein fragment (likewise claimed to enhance membrane permeability) was much less effective (data not shown). Beside mouse fibroblasts, we investigated the phalloidin derivatives in several human leukemia and lymphoma cell lines, in order to find possible specificities for one or the other kind of tumor

Partial thioamide scan on the lipopeptaibiotic trichogin GA IV. Effects on folding and bioactivity

• Marta De Zotti,
• Barbara Biondi,
• Cristina Peggion,
• Matteo De Poli,
• Haleh Fathi,
• Simona Oancea,
• Claudio Toniolo and
• Fernando Formaggio

Beilstein J. Org. Chem. 2012, 8, 1161–1171, doi:10.3762/bjoc.8.129

• -terminal 1,2-amino alcohol leucinol (Lol) by the corresponding α-amino methyl ester (Leu-OMe) alters only slightly the biophysical and biological properties of trichogin GA IV. Conversely, we showed that the Nα-blocking fatty acyl moiety plays a major role in its membrane permeability and antibiotic

• thioamide bond is present. The lowest-energy 3D structure, shown in Figure 8, exhibits the slightly amphipathic character typical of the native peptide, with the poorly hydrophilic Gly residues aligned on the same face of the helix. Membrane and biological activities The membrane permeability properties of

Volatile organic compounds produced by the phytopathogenic bacterium Xanthomonas campestris pv. vesicatoria 85-10

• Teresa Weise,
• Marco Kai,
• Anja Gummesson,
• Armin Troeger,
• Stephan von Reuß,
• Silvia Piepenborn,
• Francine Kosterka,
• Martin Sklorz,
• Ralf Zimmermann,
• Wittko Francke and
• Birgit Piechulla

Beilstein J. Org. Chem. 2012, 8, 579–596, doi:10.3762/bjoc.8.65

• levels lead to increased polyamine levels in E. coli with consequences for the membrane permeability and increased antibiotic resistance. Other volatiles such as CO, CH4, CH2O and NO were not detectable with the applied methods. However, the PTR provides evidence for the emission of sulfur-containing

(Pseudo)amide-linked oligosaccharide mimetics: molecular recognition and supramolecular properties

• José L. Jiménez Blanco,
• Fernando Ortega-Caballero,
• Carmen Ortiz Mellet and
• José M. García Fernández

Beilstein J. Org. Chem. 2010, 6, No. 20, doi:10.3762/bjoc.6.20

• expression in living cells has required the development of modified oligonucleotides as potential therapeutic agents. A key goal in the design of such agents include increasing binding affinity while maintaining sequence specificity, resistance to degradation by nucleases and improved membrane permeability

• resistant to nucleases [91][92] and the positive charge may give rise to cell membrane permeability through electrostatic attraction with the negatively charged groups of the proteoglycans at the cell surface. Using this strategy, Bruice and co-workers synthesised ribonucleic guanidine (RNG) and