Synthesis of antibacterial 1,3-diyne-linked peptoids from an Ugi-4CR/Glaser coupling approach

• Martin C. N. Brauer,
• Ricardo A. W. Neves Filho,
• Bernhard Westermann,
• Ramona Heinke and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2015, 11, 25–30, doi:10.3762/bjoc.11.4

• increasing interest to synthesize dimerized peptidomimetics with pharmacological properties through a step-efficient protocol that allows rapid access to highly diverse dimer libraries, we set out to develop a strategy based on an U-4CR/Glaser-type homocoupling sequence [34]. In comparison to popular cross

• linking reactions like, e.g., click reactions or amide bonds, the Glaser coupling allows the use of truly identical monomers. This decreases the number of steps for appropriate starting materials, and allows access to true homodimers in sensu strictu. Results and Discussion To achieve the synthesis of

Release of β-galactosidase from poloxamine/α-cyclodextrin hydrogels

• César A. Estévez,
• José Ramón Isasi,
• Eneko Larrañeta and
• Itziar Vélaz

Beilstein J. Org. Chem. 2014, 10, 3127–3135, doi:10.3762/bjoc.10.330

• kinetics [6]. The hydrophilic nature of the hydrogels is due to the presence of groups along the polymer chains such as hydroxy, carboxy, amide and sulfonic acid [7]. The cross-linking may be either physical or chemical (covalent). According to the reversible and tunable nature of self-assembly, the

Synthetic strategies for the fluorescent labeling of epichlorohydrin-branched cyclodextrin polymers

• Milo Malanga,
• Mihály Bálint,
• István Puskás,
• Kata Tuza,
• Tamás Sohajda,
• László Jicsinszky,
• Lajos Szente and
• Éva Fenyvesi

Beilstein J. Org. Chem. 2014, 10, 3007–3018, doi:10.3762/bjoc.10.319

• is in a characteristic region of the spectrum (around 56 ppm) and it does not overlap with other signals. The assignment of the C6–N3 signal can be done by cross-linking the HSQC-DEPT spectra of compound 1 and 6-monoazido-6-monodeoxy-β-CD (Supporting Information File 1, Figure S5); the assigments are

Anomalous diffusion of Ibuprofen in cyclodextrin nanosponge hydrogels: an HRMAS NMR study

• Monica Ferro,
• Franca Castiglione,
• Carlo Punta,
• Lucio Melone,
• Walter Panzeri,
• Barbara Rossi,
• Francesco Trotta and
• Andrea Mele

Beilstein J. Org. Chem. 2014, 10, 2715–2723, doi:10.3762/bjoc.10.286

• .10.286 Abstract Ibuprofen sodium salt (IP) was encapsulated in cyclodextrin nanosponges (CDNS) obtained by cross-linking of β-cyclodextrin with ethylenediaminetetraacetic acid dianhydride (EDTAn) in two different preparations: CDNSEDTA 1:4 and 1:8, where the 1:n notation indicates the CD to EDTAn molar

• behaviour can be related to the restricted diffusion of IP in the polymeric network due to the presence of nanopores originated during the cross-linking process. A visual description of the nanoporous structure of CDNSEDTA 1:4 is shown in Figure 4a. The TEM image was recorded on samples stained with Pb(NO3

• polymeric constituents. The interpretation of the superdiffusive regime observed for IP in the CDNSEDTA 1:8 is less straightforward. In order to account for the acceleration effect observed, we remind here that the cross-linking process in CDNS showed a marked dependence on the CD/cross-linker molar ratio

Encapsulation of biocides by cyclodextrins: toward synergistic effects against pathogens

• Véronique Nardello-Rataj and
• Loïc Leclercq

Beilstein J. Org. Chem. 2014, 10, 2603–2622, doi:10.3762/bjoc.10.273

• , delivery systems based on immobilized CDs provide diffusion- or affinity-controlled release kinetics. In this mechanism, the guest biocide released from one CD may become available to form new complexes with other available CDs during the diffusion through the cross-linking matrix (Scheme 8). The diffusion

Synthesis and characterization of a hyper-branched water-soluble β-cyclodextrin polymer

• Francesco Trotta,
• Fabrizio Caldera,
• Roberta Cavalli,
• Andrea Mele,
• Carlo Punta,
• Lucio Melone,
• Franca Castiglione,
• Barbara Rossi,
• Monica Ferro,
• Vincenza Crupi,
• Domenico Majolino,
• Valentina Venuti and
• Dominique Scalarone

Beilstein J. Org. Chem. 2014, 10, 2586–2593, doi:10.3762/bjoc.10.271

• concentration of monomers in the solvent phase plays a key role as well. Hyper-branched β-cyclodextrin-based polymers were obtained performing the syntheses with excess of solvent and cross-linking agent, and the conditions for critical dilution were determined experimentally. A hyper-branched polymer with very

• hydroxy groups [9] 3) inhibition of the gelation process in a sol–gel cross-linking reaction [10]. This last synthetic route leads to soluble hyper-branched polymers. According to Flory’s theory [11] gelation occurs when the branching coefficient (α) is higher than a critical value (αc) defined by the

• structural aspects and functional properties, and in particular pyromellitic nanosponges were found to present a critical cross-linking value [17]. In other words, the maximum number of cross-linkers per monomer was proved to be around 6 (i.e., 6 mol of pyromellitic dianhydride for each mol of β-CD). If the

Reversibly locked thionucleobase pairs in DNA to study base flipping enzymes

• Christine Beuck and
• Elmar Weinhold

Beilstein J. Org. Chem. 2014, 10, 2293–2306, doi:10.3762/bjoc.10.239

• the addition of thiol reagents like dithiothreitol. This property makes the cross-linking reaction fully reversible and allows for a switching of the linked base pair from locked to unlocked during biochemical experiments. Using the DNA methyltransferase from Thermus aquaticus (M.TaqI) as example, we

• derivatives and other interstrand cross-linking reagents as antitumor agents. Chemically synthesized DNA cross-links are of great interest to mimic the reaction products of cross-linking agents acting in vivo [6][7][8] and to mechanistically study enzymes that rely on opening Watson–Crick base pairs by base

• , long linkers that might interfere with protein binding are typically employed. The Verdine group has developed a cross-linking approach based on the easy postsynthetic introduction of cystamine or longer amino-alkylthiol linkers into ODN using a convertible nucleoside approach [39][40][41][42][43][44

Supercritical carbon dioxide: a solvent like no other

• Jocelyn Peach and
• Julian Eastoe

Beilstein J. Org. Chem. 2014, 10, 1878–1895, doi:10.3762/bjoc.10.196

• of worm-like micelles [50]. Worm-like micelles have been shown to build viscosity through entangling or cross-linking of the structures, which then generates a structural network and enhance elasticity and viscosity [31][50]. Micellar growth in these systems was induced through the addition of co

Multivalent scaffolds induce galectin-3 aggregation into nanoparticles

• Candace K. Goodman,
• Mark L. Wolfenden,
• Pratima Nangia-Makker,
• Anna K. Michel,
• Avraham Raz and
• Mary J. Cloninger

Beilstein J. Org. Chem. 2014, 10, 1570–1577, doi:10.3762/bjoc.10.162

• Warren Avenue, Detroit, Michigan 48201, USA 10.3762/bjoc.10.162 Abstract Galectin-3 meditates cell surface glycoprotein clustering, cross linking, and lattice formation. In cancer biology, galectin-3 has been reported to play a role in aggregation processes that lead to tumor embolization and survival

A promising cellulose-based polyzwitterion with pH-sensitive charges

• Thomas Elschner and
• Thomas Heinze

Beilstein J. Org. Chem. 2014, 10, 1549–1556, doi:10.3762/bjoc.10.159

• triethylamine deficiency conditions in order to avoid cross-linking of the polymer chains via carbonate moieties resulting from the strong basicity of the trialkylamine [22]. The aminolysis yields the (3-ethoxy-3-oxopropyl)(N-Boc-2-aminoethyl)cellulose carbamate 4 with a DSβ-alanine ester of 0.88 and a DSBoc

Synthesis and solvodynamic diameter measurements of closely related mannodendrimers for the study of multivalent carbohydrate–protein interactions

• Yoann M. Chabre,
• Alex Papadopoulos,
• Alexandre A. Arnold and
• René Roy

Beilstein J. Org. Chem. 2014, 10, 1524–1535, doi:10.3762/bjoc.10.157

• turbidimetry. The latter would allow us to measure relative kinetic factors involved in the cross-linking lattice formation using soluble partners. Results and Discussion In order to critically evaluate the subtle structural parameters imparted by glycodendrimers in deciphering their relative thermodynamic and

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• in all solvents, chemically and physically resistant and mechanically stable to allow filtration. Since peptide synthesis takes place mainly in the interior of the solid matrix, appropriate solvation, low cross linking for good accessibility and good swelling properties are very crucial. The small

• appropriate PEG units, loading and cross linking leading to elevated solubility and decreased intra- and intermolecular aggregation of the growing polypeptide [50]. The linker represents the reversible connection between the solid support and the assembling peptide. It determines the loading of the resin, the

N-Alkylated dinitrones from isosorbide as cross-linkers for unsaturated bio-based polyesters

• Oliver Goerz and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 902–909, doi:10.3762/bjoc.10.88

• isosorbide, itaconic acid and succinic acid under acid catalyzed conditions (Scheme 5). The obtained unsaturated polyester 13 showed values of 3400 g/mol and a glass transition temperature of 64 °C. The cross-linking of 10a/b with 13 was investigated by rheological measurements in oscillatory mode. The

• . The ongoing cross-linking is accompanied by restrictions in the mobility of the polymer chains and the cross-linkers, which results in lowered reaction rates with flattening values for G' and G''. Sample 10b shows a gel point at about 100 minutes, whereas the gel point of 10a shows up after 210

• present work, bio-based dinitrones were prepared from acrylated and crotonated isosorbide with benzaldoxime. They were employed as cross-linkers for unsaturated bio-based polyesters from isosorbide, itaconic acid and succinic acid. The thermal cross-linking could be followed by oscillatory measurements

Oligomeric epoxide–amine adducts based on 2-amino-N-isopropylacetamide and α-amino-ε-caprolactam: Solubility in presence of cyclodextrin and curing properties

• Julian Fischer and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 2803–2811, doi:10.3762/bjoc.9.315

• material. Also, because of its high thermosensitivity and tendency of cross linking on heating, mass spectrometry data were not useful for determination of that molecular weights. However, DLS measurements gave hydrodynamic diameters of 2.7 nm for 9 and 2.4 nm for 10 (Supporting Information File 1). This

The application of a monolithic triphenylphosphine reagent for conducting Ramirez gem-dibromoolefination reactions in flow

• Kimberley A. Roper,
• Malcolm B. Berry and
• Steven V. Ley

Beilstein J. Org. Chem. 2013, 9, 1781–1790, doi:10.3762/bjoc.9.207

• convective flow-through the macropores, as well as providing lower void volumes [16]. Practically, their rigid structure is secure over a wide range of solvents and under reasonable pressures compared to beads due to a high degree of cross linking, making them advantageous when applied to flow processes [21

• precipitation polymerisation of the phosphine monomer 5 (Scheme 2). A polymerisation mixture of the triphenylphosphine monomer 5, cross-linking components divinylbenzene (6) and styrene (7) along with the porogen, 1-dodecanol (8), was heated to 50 °C until a homogeneous mixture was achieved. The initiator

Polymeric redox-responsive delivery systems bearing ammonium salts cross-linked via disulfides

• Christian Dollendorf,
• Martin Hetzer and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 1652–1662, doi:10.3762/bjoc.9.189

• -methacryloylglycylglycine, copolymers of DMAEMA and 1,4-bis(2-thiobenzoylthio)prop-2-yl)benzene, or cross-linked poly(L-lysine) [46][47][48]. In the current work, we describe the synthesis of a novel redox-responsive polycationic hydrogel by cross-linking copolymers of N,N-diethylacrylamide (DEAAm) and DMAEMA with a

• disulfide-bearing cross-linking agent. The redox-responsive behavior of the cross-linked poly(DEAAm-co-DMAEMA) hydrogel was shown by reversible enclosure and release of different dyes and further proven by rheological measurements. Additionally, physical properties of the cationic hydrogels, e.g., glass

• :1). Quantitative conversions were reached. Solutions with higher concentrations led to higher molecular weights during the reaction, but also to broader weight distributions (refer to Table 1). The cross-linking agent N,N’-bis(4-chlorobutanoyl)cystamine (CL 1) was synthesized by using the reaction

Aqueous reductive amination using a dendritic metal catalyst in a dialysis bag

• Jorgen S. Willemsen,
• Jan C. M. van Hest and
• Floris P. J. T. Rutjes

Beilstein J. Org. Chem. 2013, 9, 960–965, doi:10.3762/bjoc.9.110

• ). The first step involved demethylation of 4,4’-dimethoxy-2,2’-bipyridine (1) in 92% yield [31]. Monofunctionalization of the ligand will lead to the highest possible catalyst loading per dendrimer and also prevents cross-linking between dendrimers. Therefore, a 1:1 mixture of isopropyl mesylate (5) and

Polymerization of novel methacrylated anthraquinone dyes

• Christian Dollendorf,
• Susanne Katharina Kreth,
• Soo Whan Choi and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 453–459, doi:10.3762/bjoc.9.48

• emplaced into several copolymers. Due to two polymerizable functionalities, they can act as cross-linking agents. Thus, diffusion out of the polymer can be avoided, which increases the physiological compatibility and makes the dyes promising compounds for medical applications, such as iris implants

• chloride always leads to the formation of several side-products. As cross-linking agent, 2 can be copolymerized with other methacrylate- or acrylate-comonomers, to build up macromolecules bearing covalently emplaced dye derivatives. The UV–vis spectra of 1 and 2 (Figure 1a) in each case show three

• also be used as a cross-linking agent. For this purpose, 1-chloroanthraquinone was coupled with 2-amino-2-methyl-1,3-propanediol under argon atmosphere and esterified with methacryloyl chloride to obtain 15 (Scheme 1, step g), which absorbs light at 495 nm. In the absence of argon, the formation of a

Development of peptidomimetic ligands of Pro-Leu-Gly-NH₂ as allosteric modulators of the dopamine D₂ receptor

• Swapna Bhagwanth,
• Ram K. Mishra and
• Rodney L. Johnson

Beilstein J. Org. Chem. 2013, 9, 204–214, doi:10.3762/bjoc.9.24

• , Figure 3) [3][36]. These photoaffinity ligands were found to retain the ability to modulate dopamine receptors to varying degrees, thus indicating that the incorporation of the photoreactive moieties did not have a significantly adverse effect on ligand binding to the modulatory site. Cross-linking of

Cyclodextrin-based nanosponges as drug carriers

• Francesco Trotta,
• Marco Zanetti and
• Roberta Cavalli

Beilstein J. Org. Chem. 2012, 8, 2091–2099, doi:10.3762/bjoc.8.235

• swelling properties. The polarity and dimension of the polymer mesh can be easily tuned by varying the type of cross-linker and degree of cross-linking. Nanosponge functionalisation for site-specific targeting can be achieved by conjugating various ligands on their surface. They are a safe and

• by reacting native cyclodextrins with a cross-linking agent that, after reaction, exerts its own properties and influences the behaviour of the cyclodextrin unit. Although insoluble cross-linked cyclodextrin polymers were first reported a long time ago, by reacting the parent cyclodextrin with

• , cross-linked with a suitable cross-linking agent. Interesting results have already been obtained as drug carriers by using an active carbonyl compound, e.g., carbonyldimiidazole, triphosgene, diphenyl carbonate, or organic dianhydrides (Scheme 1). Detailed reaction conditions and parameters are reported

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

• ; solution B: 0.059% TFA in 80% acetonitrile). The elution was monitored at 214 nm. The peptides were assayed for purity by analytical HPLC and ESIMS. The peptides were coupled to aminophalloidin through the hetero-bifunctional cross-linking agent SPDP (3-(2-pyridyldithio)propionic acid N-hydroxysuccinimide

• = 27500), and monomethoxy-polyethyleneglycolamine (Mr = 810, 5200, 22600) were coupled to aminophalloidin by the amine-reactive homo-bifunctional cross-linking reagents DSP (dithiobis(succinimidylpropionate); Lomant’s reagent) with cleavable disulfide group, or DSS (disuccinimidyl suberate) containing a

Mannose-decorated cyclodextrin vesicles: The interplay of multivalency and surface density in lectin–carbohydrate recognition

• Ulrike Kauscher and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2012, 8, 1543–1551, doi:10.3762/bjoc.8.175

• adamantane) were added to cyclodextrin vesicles (0.2 mM) an aggregation effect was detected even in the absence of ConA (Figure 5). This effect is due to noncovalent cross-linking of the vesicles by guest 2–4. Each of the adamantane units on guest 2–4 can bind to a different cyclodextrin vesicle

• (intervesicular binding) and hence cause vesicle aggregation. We have previously observed this effect for homobifunctional guest molecules equipped with two azobenzene, methylbenzoyl, or tert-butylbenzyl groups [32][33][34]. It should be noted that in the case of guest 3 the aggregation due to cross-linking is

• ) results in a complete suppression of cross-linking of the vesicles. Apparently, at this concentration intravesicular binding is favored over intervesicular binding, and vesicle aggregation is negligible. These findings are again consistent with earlier observations [32]. Hence, in this concentration

Cyclodextrin nanosponge-sensitized enantiodifferentiating photoisomerization of cyclooctene and 1,3-cyclooctadiene

• Wenting Liang,
• Cheng Yang,
• Masaki Nishijima,
• Gaku Fukuhara,
• Tadashi Mori,
• Andrea Mele,
• Franca Castiglione,
• Fabrizio Caldera,
• Francesco Trotta and
• Yoshihisa Inoue

Beilstein J. Org. Chem. 2012, 8, 1305–1311, doi:10.3762/bjoc.8.149

• used as a descriptor of the degree of cross linking and the elastic properties [42]. By using Raman and Brillouin scattering experiments, we found that increasing the PMA/CD ratio leads to an increase in the degree of cross linking, with the frequency of the maximum boson peak in cross-polarized Raman

Combined bead polymerization and Cinchona organocatalyst immobilization by thiol–ene addition

• Kim A. Fredriksen,
• Tor E. Kristensen and
• Tore Hansen

Beilstein J. Org. Chem. 2012, 8, 1126–1133, doi:10.3762/bjoc.8.125

• 4–9, thereby adjusting the degree of cross-linking. As for the Cinchona organocatalysts, we wanted to incorporate either unmodified quinine (1), the primary amine organocatalyst 2, or thiourea organocatalyst 3 into the thiol–ene network (Figure 1). While quinine is available directly, primary amine

• in several organic solvents, particularly in THF and CH2Cl2, despite their significant degree of cross-linking. As such, they have much in common with the CLEAR (cross-linked ethoxylate acrylate resin) resins, a type of polymer support with all the characteristics of a microporous polymer that also

• has an unusually high degree of cross-linking [16]. Unlike vinyl ether 6 and allyl ether 9, acrylic building blocks such as 7 and 8 may undergo some degree of acrylic homopolymerization during network formation, although the thiol–ene addition is usually more rapid than the polymerization. The ratio

High-affinity multivalent wheat germ agglutinin ligands by one-pot click reaction

• Henning S. G. Beckmann,
• Heiko M. Möller and
• Valentin Wittmann

Beilstein J. Org. Chem. 2012, 8, 819–826, doi:10.3762/bjoc.8.91

• mentioning that we never observed precipitate formation during incubation of WGA with our synthetic ligands. This suggests that in our case intermolecular multivalency (cross-linking) plays a negligible role and that the main mechanism of affinity enhancement is chelating binding to the same WGA dimer. The