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

• , 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

• its neighboring base pairs. In contrast, the ideal geometry of saturated linkers will demand non-planar torsion angles. Coleman et al. [44] investigated this topic by performing molecular dynamic simulations for a disulfide cross-linked I6S/U4S base pair in B-DNA and showed that the compromise between

Molecular recognition of AT-DNA sequences by the induced CD pattern of dibenzotetraaza[14]annulene (DBTAA)–adenine derivatives

• Marijana Radić Stojković,
• Marko Škugor,
• Łukasz Dudek,
• Jarosław Grolik,
• Julita Eilmes and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2175–2185, doi:10.3762/bjoc.10.225

• stacked dimers within the DNA minor groove similar to the crystal structure of close analogue (Figure 4, right). Conversely, the AP5 and AP6 aliphatic linkers are long enough to allow self-folding and easy intramolecular π–π stacking of adenine with DBTAA (Figure 4, upper right). During the binding event

Macrocyclic bis(ureas) as ligands for anion complexation

• Claudia Kretschmer,
• Gertrud Dittmann and
• Johannes Beck

Beilstein J. Org. Chem. 2014, 10, 1834–1839, doi:10.3762/bjoc.10.193

• ring with two ethynylene groups as linkers and 2 the larger ring with two butadiynylene groups. On thermal treatment to 130 °C molecule 1 splits up into two dihydroindoloquinolinone (3) molecules. Both compounds 1 and 2 form adducts with polar molecules such as dimethyl sulfoxide (DMSO) and

• planar ligand, as was shown by indole-based macrocycles [9]. This ligand system represents a stiff ring of two bis(indole) units connected via two ethynylene groups as linkers. As proven by a crystal structure determination, a chloride ion fits into the cavity bound via four N−H∙∙∙Cl bonds and strong

• butadiynylene groups as spacers turned out as a suitable receptor for small anions with high binding constants. The molecule is flexible. In the complex with a bromide ion embedded in the ring cavity, the cyclic ligand is strongly tilted. The smaller cycle with ethynylene groups as linkers is a much weaker

Influence of perylenediimide–pyrene supramolecular interactions on the stability of DNA-based hybrids: Importance of electrostatic complementarity

• Christian B. Winiger,
• Simon M. Langenegger,
• Oleg Khorev and
• Robert Häner

Beilstein J. Org. Chem. 2014, 10, 1589–1595, doi:10.3762/bjoc.10.164

• (Table 1, hybrids 1*2 and 7*6) than hybrids containing both types of aromatic compounds. Although the actual stability of such duplexes strongly depends on several parameters like, e.g., the geometry of the building blocks and the flexibility of the linkers, a general trend can be deduced from the

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

• moieties and an aromatic central core but the introduction of distinct functionalized linkers may change the overall hydrophobic/hydrophilic balances of the structures. As such, they could engage supplementary intramolecular hydrogen bonding or hydrophobic interactions that could mediate their three

• ranging from 1.51 to 1.33 × 10−10 m2s−1 for protons in the core or the periphery. Interestingly, calculation of the extended conformation (MM2, Chem3D) of the linkers in 12, 17, and 21 showed lengths of 14.8, 17.1, and 21.8 Å, respectively. Conclusion The syntheses of three related families of

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• protonable amines into neutral amide or carbamate linkers. Even though PEGylation of chitosan via the amino group is the most commonly used method a number of examples of polysaccharide derivatisation on the hydroxy groups have been reported. Chitosan-O-poly(ethylene glycol) graft copolymers were synthesized

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

• ) group [43]). For a precise overview, the review of Isidro-Llobet 2009 and detailed manuals of major companies are recommended [44][45][46]. Optimal resins and linkers for peptide synthesis: The solid phase has to meet a number of requirements to be suitable for peptide synthesis. It has to be insoluble

• . recently published a collection of commonly used resins, together with their individual swelling and loading (is defined by the equivalents of amino acid in mmol/g, which can be attached to the resin) properties [50]. With respect to PEG-functionalized linkers, peptide synthesis yields can be improved by

• -terminus can be modified as hydrazide, alcohol, aldehyde, thioester and many more [22][50]. Furthermore, there are linkers that enable the synthesis of partially and fully protected peptides such as the 2-chlorotrityl resin [51] or the Sieber amide resin [52]. Consequently, the choice of resin and linker

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

• ) were used as model systems and reacted with dimethyl itaconate to further characterize the 1,3-dipolaric cycloaddition. Keywords: bio-based polyesters; cross-linkers; dinitrones; 1,3-dipolar cycloaddition; isosorbide; Introduction Nitrones represent a class of compounds with a versatile use as

• synthesis of polymers bearing nitrones as photosensitive material [7][8] was also described. We focused on the preparation of polynitrones as efficient cross-linkers for unsaturated polyesters based on fumaric und maleic acid [9]. In the light of the growing interest in polymers from renewable resources the

• synthesis of bio-based nitrones as novel cross-linkers for unsaturated bio-polyesters [10] offers an interesting access to biocompatible materials. This paper presents the synthesis of bio-based N-alkylated dinitrones based on isosorbide and the subsequent use of these dinitrones as cross-linkers in a 1,3

Staudinger ligation towards cyclodextrin dimers in aqueous/organic media. Synthesis, conformations and guest-encapsulation ability

• Malamatenia D. Manouilidou,
• Yannis G. Lazarou,
• Irene M. Mavridis and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 774–783, doi:10.3762/bjoc.10.73

• couplings [16][23], the classical formation of ester [12][17], amide [25][26] or imide [27] bonds between CDs or amino CDs and acid- or anhydride-linkers, and finally urea/thiourea bonds [28][29]. However, the obvious advantages of the Staudinger ligation (high reaction rates, absence of a catalyst, aqueous

•  1, Figure S1). Compound 3 showed a single methoxy group in the 1H NMR spectrum (3.57 ppm) and a single carbonyl signal in the 13C NMR spectrum (166.8 ppm), reflecting the compound’s high molecular symmetry. Both linkers were stored under argon at −20 °C to minimize oxidation, although best results

• studied the mechanism of the Staudinger ligation of arylphosphine ester linkers such as 2 with various alkyl azide substrates [7]. They have shown that the ligation is a second order process: polar protic solvents and electron-donating substituents on the aryphosphine accelerate the reaction, while the

Preparation of new alkyne-modified ansamitocins by mutasynthesis

• Kirsten Harmrolfs,
• Lena Mancuso,
• Binia Drung,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2014, 10, 535–543, doi:10.3762/bjoc.10.49

• that a release mechanism of the cytotoxin is part of the molecular architecture of the conjugate [31]. Disulfide linkers have shown to be well suited when utilizing the reducing power between extra- and intracellular milieus which results in cleavage and liberation of the drug. Mitomycin conjugates [32

Studies toward bivalent κ opioids derived from salvinorin A: heteromethylation of the furan ring reduces affinity

• Thomas A. Munro,
• Wei Xu,
• Douglas M. Ho,
• Lee-Yuan Liu-Chen and
• Bruce M. Cohen

Beilstein J. Org. Chem. 2013, 9, 2916–2924, doi:10.3762/bjoc.9.328

• ligands with a furanylmethyl substituent (Figure 3), we decided to use a short linker. As an alternative approach, bivalent ligands with much longer linkers can bind simultaneously to both protomers in a receptor dimer, allowing selective targeting of specific receptor oligomers [21]. We also sought to

• provide a suitable attachment point for such linkers based on our previous studies of C-2 alkoxymethyl ethers [22][23], which have higher tolerance to alkyl chain extension [24] than other derivatives of 1 [1]. Results Synthesis Initial attempts to form the 16-dimethylaminomethyl derivative 2 by treatment

• is thus not a promising attachment point. At the opposite extreme, the C-2 alkoxymethyl ether series is highly tolerant to alkyl chain extension. Compound 6 and the synthetic route used may prove useful for the attachment of very long linkers, as used with other scaffolds to bridge receptor dimers

Synthesis of nucleotide–amino acid conjugates designed for photo-CIDNP experiments by a phosphotriester approach

• Tatyana V. Abramova,
• Olga B. Morozova,
• Vladimir N. Silnikov and
• Alexandra V. Yurkovskaya

Beilstein J. Org. Chem. 2013, 9, 2898–2909, doi:10.3762/bjoc.9.326

• conjugates consisting of amino acid, nucleotide, and dye residues including linkers of different lengths (Figure 1). Target compounds 1–8 have been synthesized by the phosphotriester block liquid phase synthesis (LPS). Results and Discussion Design of model compounds Our previous studies revealed a great

Gold(I)-catalyzed hydroarylation reaction of aryl (3-iodoprop-2-yn-1-yl) ethers: synthesis of 3-iodo-2H-chromene derivatives

• Pablo Morán-Poladura,
• Eduardo Rubio and
• José M. González

Beilstein J. Org. Chem. 2013, 9, 2120–2128, doi:10.3762/bjoc.9.249

• , two facts are of mechanistic significance. First, the 2:3 ratio for a given R substituent (Scheme 4A, R = 4-Cl) can be compared for the two linkers. For the nitrogen-containing tether (X = NTs, Scheme 4A), almost exclusive formation of 2 was noticed (reaction in 1,2-dichloroethane, at rt for 24 h, [43

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

• or CL 2, or both cross-linkers (Scheme 2). Rheological measurements of cross-linked polymer discs To investigate the rheological characteristics of cross-linked polycationic hydrogels, polymer discs of poly(DEAAm-co-DMAEMA, 1:1) containing between 1.0 and 5.0 mol % of either CL 1 (samples 4), or CL 2

• (samples 5), or both cross-linkers (samples 6) were synthesized. The samples were immersed in distilled water until the equilibrium state of swelling was reached. The swollen samples were then used for oscillatory measurements using the serrated plate–plate geometry. As expected, the storage modulus G

• the enhanced affinity for interactions with water molecules leads to a better enclosure of water and therefore a higher swelling degree. Sample 6, which contains both cross-linkers, shows the lowest values for Q. This can be attributed to its overall higher content of cross-linker, compared to samples

Molecular assembly of amino acid interlinked, topologically symmetric, π-complementary donor–acceptor–donor triads

• M. B. Avinash,
• K. V. Sandeepa and
• T. Govindaraju

Beilstein J. Org. Chem. 2013, 9, 1565–1571, doi:10.3762/bjoc.9.178

• acids as linkers is due to their compactness, variable side chain functionality and sequence-specific self-assembling properties and the desire to exploit their inherent chiral information for helical assembly of electro-active molecular materials [35][36][37][38][39][40][41][42][43][44][45][46][47][48

Synthesis and evaluation of cell-permeable biotinylated PU-H71 derivatives as tumor Hsp90 probes

• Tony Taldone,
• Anna Rodina,
• Erica M. DaGama Gomes,
• Matthew Riolo,
• Hardik J. Patel,
• Raul Alonso-Sabadell,
• Danuta Zatorska,
• Maulik R. Patel,
• Sarah Kishinevsky and
• Gabriela Chiosis

Beilstein J. Org. Chem. 2013, 9, 544–556, doi:10.3762/bjoc.9.60

• compounds that demonstrate such combined properties (Figure 1). As such we have prepared a number of biotinylated analogues, derived from 1a and 1b, containing linkers of various lengths (1 to 17 atoms) and hydrophobicities (polyethylene-, amide- and/or alkyl-containing). In addition, an amine-linked biotin

• essential that the linker be of sufficient length to enable the concomitant binding to Hsp90 and streptavidin, it is also important that it is not exceedingly long for two reasons. First, the possibility and extent of nonspecific binding increases with longer linkers. Second, longer linkers result in a

• ), despite the fact that both 1a and 1b bound Hsp90 with similar affinity (24.5 versus 26 nM for 1a and 1b, respectively). This is likely a result of increased steric crowding of the bulky isopropyl group in analogues of 1a. Second, in terms of the linkers, the carbon series appeared to have a somewhat

Spin state switching in iron coordination compounds

• Philipp Gütlich,
• Ana B. Gaspar and
• Yann Garcia

Beilstein J. Org. Chem. 2013, 9, 342–391, doi:10.3762/bjoc.9.39

Towards a biocompatible artificial lung: Covalent functionalization of poly(4-methylpent-1-ene) (TPX) with cRGD pentapeptide

• Lena Möller,
• Christian Hess,
• Jiří Paleček,
• Yi Su,
• Axel Haverich,
• Andreas Kirschning and
• Gerald Dräger

Beilstein J. Org. Chem. 2013, 9, 270–277, doi:10.3762/bjoc.9.33

• fluorescein R5N3 9 for analytic purposes. Supporting Information Details on the synthesis and analyses of building blocks and linkers, functionalization, biological evaluation and descriptions of analyses of TPX materials based on XPS, UV, IR and contact-angle measurements are found in Supporting Information

Glycosylation efficiencies on different solid supports using a hydrogenolysis-labile linker

• Mayeul Collot,
• Steffen Eller,
• Markus Weishaupt and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 97–105, doi:10.3762/bjoc.9.13

• /bjoc.9.13 Abstract Automated oligosaccharide assembly requires suitable linkers to connect the first monosaccharide to a solid support. A new hydrogenolysis-labile linker that is stable under both acidic and basic conditions was designed, synthesized and coupled to different resins. Glycosylation and

• cleavage efficiencies on these functionalized solid supports were investigated, and restrictions for the choice of solid support for oligosaccharide synthesis were found. Keywords: glycosylation; hydrogenolysis; linkers; oligosaccharides; resins; solid-phase synthesis; Findings Since Bruce Merrifield

• , were introduced. To perform enzymatic reactions on a solid support, nonswelling resins (Synbeads) with large surfaces and big cavities that can be accessed even by proteins were developed [36]. For the design of linkers for oligosaccharide synthesis on solid support, several key features have to be

An improved synthesis of a fluorophosphonate–polyethylene glycol–biotin probe and its use against competitive substrates

• Hao Xu,
• Hairat Sabit,
• Gordon L. Amidon and
• H. D. Hollis Showalter

Beilstein J. Org. Chem. 2013, 9, 89–96, doi:10.3762/bjoc.9.12

• competed out with the active enzyme covalently linked to the probe, even though the concentration of added substrate is high compared to the probe. Enzymes have different kinetic properties in the same proteome sample, and a single enzyme can have different preferences for FP probes with different linkers

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

• disulfide-containing linkers, which would be reduced inside the cell so as to release a defined thiol derivative of phalloidin (Table 1). Actin binding All phalloidin derivatives were tested for their affinity to muscle actin (α-actin), which is used as a model for β-actin present in nonmuscle cells. This

• been described as a method to improve the solubility of drugs, prolong their half-lives in plasma, or modulate their pharmacokinetics [35]. An effect not described to our knowledge so far is that pegylation can enhance, several hundred-fold, the penetration of a hydrophilic drug into cells. Linkers

Acylsulfonamide safety-catch linker: promise and limitations for solid–phase oligosaccharide synthesis

• Jian Yin,
• Steffen Eller,
• Mayeul Collot and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 2067–2071, doi:10.3762/bjoc.8.232

• Abstract Safety-catch linkers are useful for solid-phase oligosaccharide synthesis as they are orthogonal to many common protective groups. A new acylsulfonamide safety-catch linker was designed, synthesized and employed during glycosylations using an automated carbohydrate synthesizer. The analysis of the

• ] afforded linker 10. To support oligosaccharide synthesis, the safety-catch linker was first coupled to different resins (Scheme 2). In addition, since the activation and cleavage of safety-catch linkers is typically quite slow, a second, base-labile (Zemplén [24]) cleavage site was integrated to facilitate

• , the amount of glycosylating agent was decreased during a reaction, which resulted in the production of glycosylated linkers 21 and 22. It was evident that two unexpected reactions had occurred. First, the use of excess glycosylating agent, common practice for solid-phase-synthesis protocols, leads to

Modulating the activity of short arginine-tryptophan containing antibacterial peptides with N-terminal metallocenoyl groups

• H. Bauke Albada,
• Alina-Iulia Chiriac,
• Michaela Wenzel,
• Maya Penkova,
• Julia E. Bandow,
• Hans-Georg Sahl and
• Nils Metzler-Nolte

Beilstein J. Org. Chem. 2012, 8, 1753–1764, doi:10.3762/bjoc.8.200

• linkers, a set of peptides were prepared (Table 1 and Figure 1). These peptides were obtained after acidic cleavage of the resin-bound protected precursors, purified by preparative HPLC, and the fractions containing the desired compound in high purity were lyophilized from the prep-HPLC buffers. All these

Supramolecular hydrogels formed from poly(viologen) cross-linked with cyclodextrin dimers and their physical properties

• Yoshinori Takashima,
• Yang Yuting,
• Miyuki Otsubo,
• Hiroyasu Yamaguchi and
• Akira Harada

Beilstein J. Org. Chem. 2012, 8, 1594–1600, doi:10.3762/bjoc.8.182

• tertiary gels, which should create a new paradigm in materials science [10]. Polyrotaxanes form topological gels, because the rotor molecules, which act as cross-linkers, slide on the axial polymer chain. In contrast, chemical gels do not exhibit cross-linker slippage. Previously, there have been some

Synthesis of chiral sulfoximine-based thioureas and their application in asymmetric organocatalysis

• Marcus Frings,
• Isabelle Thomé and
• Carsten Bolm

Beilstein J. Org. Chem. 2012, 8, 1443–1451, doi:10.3762/bjoc.8.164

• additional stereogenic centers, alternative molecules with substituted ethylene linkers ((SS,SC)-18 and (RS,SC)-19) were designed. Their syntheses are outlined in Scheme 5, which also underlines the value of the highly modular preparative approach towards such compounds leading to a variety of molecules by

• on the stereochemistry-determining path despite the fact that they were relatively close to the thiourea substrate binding site. Thus, reducing molecular flexibility by incorporation of plain arenes as linkers appears to be more important than conformational fixation through additional stereogenic