Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• aim to facilitate structural modifications in DNA and RNA targeting by oligo-aryl derivatives, new amino acids with phenanthridine attached to the side chain were prepared and the solid phase synthesis of novel peptide-bridged bis-phenanthridine derivatives was developed (Figure 4) [68], whereby the

• structural explanation of observed ICD recognition. Laborious synthetic procedures for the preparation of bis-phenanthridine–nucleobase conjugates initiated a novel, convergent and much more flexible approach relying on solid phase peptide synthesis described earlier (Figure 4). In such a manner prepared

Nucleic acid chemistry

• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2014, 10, 2928–2929, doi:10.3762/bjoc.10.311

• phosphordiesters or -triesters. Finally, this approach using phosphoramidites as nucleoside building blocks was significantly further developed in 1981 by Beaucage and Caruthers [4]. Since then, oligonucleotides of up to 50-mers in length have become available by an extremely efficient solid-phase methodology that

Synthesis of nanodiamond derivatives carrying amino functions and quantification by a modified Kaiser test

• Gerald Jarre,
• Steffen Heyer,
• Elisabeth Memmel,
• Thomas Meinhardt and
• Anke Krueger

Beilstein J. Org. Chem. 2014, 10, 2729–2737, doi:10.3762/bjoc.10.288

• test on residual amino groups of amino acids in solid-phase supported peptide synthesis. A report on a quantitative variation of the Kaiser test was published by Sarin et al. [23]. As this assay is colorimetric, its execution is very convenient. One limitation of the method, though, is the restriction

Versatile synthesis of amino acid functionalized nucleosides via a domino carboxamidation reaction

• Vicky Gheerardijn,
• Jos Van den Begin and
• Annemieke Madder

Beilstein J. Org. Chem. 2014, 10, 2566–2572, doi:10.3762/bjoc.10.268

• enabled by techniques such as solid phase synthesis, post synthetic modifications or enzymatic incorporation of modified analogues. Originating from research into aptamers as strong and selective binders [12][13][14], several research groups are investigating the creation and synthesis of new DNA or RNA

• have a stable and predictable structure allowing the design of engineered active sites through the carefully planned introduction of extra catalytic functionalities via solid phase DNA synthesis. We have further recently shown that the combination of solid phase synthesis and molecular modeling

• functionalized amino acids onto nucleoside building blocks (Figure 1). Following the event of solid phase peptide synthesis, a large range of amino acids with different protection schemes and stereochemistry is currently commercially available. We here illustrate a methodology for direct incorporation of amino

Synthesis of aromatic glycoconjugates. Building blocks for the construction of combinatorial glycopeptide libraries

• Markus Nörrlinger and
• Thomas Ziegler

Beilstein J. Org. Chem. 2014, 10, 2453–2460, doi:10.3762/bjoc.10.256

• were used for combinatorial solid phase or automated spot synthesis of libraries of highly glycosylated peptides and shown to specifically bind to lectins [5][8][10]. Here, we now describe the preparation of a series of glycopeptide building blocks which allow for the construction of glycopeptide

• of the two gluco-dipeptides were only in the medium range due to traces of unidentified byproducts which could not easily removed during chromatographic purification. Nevertheless, the only medium yields in this case can be circumvented in solid phase syntheses of such glycopeptides where an excess

• of one building block can be applied and no chromatographic purification is necessary. Such combinatorial solid phase syntheses with the building blocks described here are now underway. Conclusion We have described the preparation of a series of new aromatic glycopeptoids and have demonstrated their

Towards the sequence-specific multivalent molecular recognition of cyclodextrin oligomers

• Michael Kurlemann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 2428–2440, doi:10.3762/bjoc.10.253

• Supporting Information File 1). The di- and trivalent guest strands 8–14 (Figure 1C, D) were synthesized by solid phase peptide synthesis using a standard Fmoc-protocol (Figure 3). Therefore the serine derivatives 15 and 16 (Figure 1E) and a water-soluble linker molecule were used. The purity of the guest

• ). Synthesis of the di- and trivalent CD sequences 1–7 (for detailed reaction conditions see Supporting Information File 1). Solid phase peptide synthesis of the di- and trivalent guest strands 8 – 14 (for detailed reaction conditions see Supporting Information File 1). 1H NMR spectra of 17 (B) and its

Synthesis of novel conjugates of a saccharide, amino acids, nucleobase and the evaluation of their cell compatibility

• Dan Yuan,
• Xuewen Du,
• Junfeng Shi,
• Ning Zhou,
• Abdulgader Ahmed Baoum and
• Bing Xu

Beilstein J. Org. Chem. 2014, 10, 2406–2413, doi:10.3762/bjoc.10.250

• synthesis of a novel type of conjugate of three fundamental biological build blocks (i.e., saccharide, amino acids, and nucleobase) and their cell compatibility. The facile synthesis starts with the synthesis of nucleobase and saccharide derivatives, then uses solid-phase peptide synthesis (SPPS) to build

• . Synthesis Schemes 1–4 show the syntheses of the SAN conjugates formed by the reaction of the amino acid segment with the nucleobase and the saccharide derivative. The key steps include N-alkylation, acetylation, solid-phase peptide synthesis (SPPS) and N-hydroxysuccinimide (NHS)/N,N-diisopropylcarbodiimide

• 12, 16, and 19. Solid-phase peptide synthesis of peptide segment Fmoc-naphthAla-Phe-Arg(pbf)-Gly-Asn(Ot-Bu)-OH (20). Synthesis of H-naphthAla-Phe-Arg(pbf)-Gly-Asn(Ot-Bu)-adenine (22). Synthesis of saccharide–amino acids–nucleobase conjugate 3. Supporting Information Supporting Information File 432

Autonomous assembly of synthetic oligonucleotides built from an expanded DNA alphabet. Total synthesis of a gene encoding kanamycin resistance

• Kristen K. Merritt,
• Kevin M. Bradley,
• Daniel Hutter,
• Mariko F. Matsuura,
• Diane J. Rowold and
• Steven A. Benner

Beilstein J. Org. Chem. 2014, 10, 2348–2360, doi:10.3762/bjoc.10.245

• long DNA (L-DNA) constructs from short synthetic DNA fragments, which are today quite inexpensive because of automated solid-phase synthesis. However, the low information density of DNA built from just four nucleotide “letters”, the presence of strong (G:C) and weak (A:T) nucleobase pairs, the non

• systems; solid-phase DNA synthesis; synthetic biology; Introduction It has been nearly 50 years since the first solid-phase synthesis of DNA by Letsinger and Mahadevan [1][2]. This work laid the platform for new strategies in oligonucleotide synthesis, culminating in the development of phosphoramidite

• to assist in downstream processing. Thus, the complete target L-DNA sequence had 863 base pairs. Synthesis The oligonucleotides containing S and B shown in Table 1 were obtained from IDT, where they were prepared by automated solid phase phosphoramidite-based synthesis following the procedure of

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

• extrahelical side and thus has an important contribution to the overall DNA-binding energy of M.TaqI. Experimental Solid-phase DNA synthesis was performed on an ABI DNA Synthesizer 392 in 1 µmol scale following the standard cycles recommended by Applied Biosystems with a coupling time of 30 s for the natural

Solution phase synthesis of short oligoribonucleotides on a precipitative tetrapodal support

• Alejandro Gimenez Molina,
• Amit M. Jabgunde,
• Pasi Virta and
• Harri Lönnberg

Beilstein J. Org. Chem. 2014, 10, 2279–2285, doi:10.3762/bjoc.10.237

• , dynamics of chain invasion and recognition by small molecular entities [6][7][8][9][10]. The quantities of short RNA sequences required for such studies are often larger than what can easily be obtained by lab-scale solid phase synthesis. In other words, there seems to be a need for a straightforward

Synthesis and optical properties of pyrrolidinyl peptide nucleic acid carrying a clicked Nile red label

• Nattawut Yotapan,
• Chayan Charoenpakdee,
• Pawinee Wathanathavorn,
• Boonsong Ditmangklo,
• Hans-Achim Wagenknecht and
• Tirayut Vilaivan

Beilstein J. Org. Chem. 2014, 10, 2166–2174, doi:10.3762/bjoc.10.224

• under different sequence context, were successfully synthesized and characterized by MALDI–TOF MS (Figure 1 and Table 1). Isolated yields in the range of 6–18% were obtained (0.5 μmol scale), which are typical for solid phase synthesis, whereby the majority of material loss occurred during HPLC

Second generation silver(I)-mediated imidazole base pairs

• Susanne Hensel,
• Nicole Megger,
• Kristina Schweizer and
• Jens Müller

Beilstein J. Org. Chem. 2014, 10, 2139–2144, doi:10.3762/bjoc.10.221

• shows silver(I)-mediated methylimidazole homo base pairs involving either 2-methylimidazole (top) or 4-methylimidazole (bottom), resulting in a shielded access to the silver(I) ions from the minor and major groove, respectively. The phosphoramidites required for automated DNA solid-phase synthesis were

• the two hydroxy functions with the dimethoxytrityl and the 2-cyanoethyl-N,N-diisopropylphosphoramidite moieties, finally resulting in the formation of 4a/4b suitable for automated solid-phase oligonucleotide synthesis. The pKa values of the free nucleosides 2a/2b were determined by pD-dependent 1H NMR

• ) ions from minor and major groove, respectively. Synthesis of methylimidazole-based nucleosides and their corresponding phosphoramidites required for automated solid-phase DNA synthesis. a) 1. NaH, 2. Hoffer’s chloro sugar, CH3CN, 0 °C to ambient temperature, 3 h; b) aqueous NH3 (25%), CH3OH, ambient

Synthesis of phosphoramidites of isoGNA, an isomer of glycerol nucleic acid

• Keunsoo Kim,
• Venkateshwarlu Punna,
• Phaneendrasai Karri and
• Ramanarayanan Krishnamurthy

Beilstein J. Org. Chem. 2014, 10, 2131–2138, doi:10.3762/bjoc.10.220

• triethylamine·HF complex instead of TBAF was preferable at room temperature. The free alcohols 12, 18, 21 and 24 were phosphitylated under standard conditions to obtain the phosphoramidites suitable for the automated solid phase synthesis. Conclusion We have described herein improvements to and the optimization of

Synthesis of a bifunctional cytidine derivative and its conjugation to RNA for in vitro selection of a cytidine deaminase ribozyme

• Nico Rublack and
• Sabine Müller

Beilstein J. Org. Chem. 2014, 10, 1906–1913, doi:10.3762/bjoc.10.198

• confirmed by successful conjugation to the 3'-terminus of a model RNA, as analyzed by HPLC and MALDI–MS. This set-up is going to be used for selection of a cytidine deaminase ribozyme supporting the conversion of uridine to cytidine. Active molecules will be cleaved from the solid phase and released into

Convergent synthetic methodology for the construction of self-adjuvanting lipopeptide vaccines using a novel carbohydrate scaffold

• Vincent Fagan,
• Istvan Toth and
• Pavla Simerska

Beilstein J. Org. Chem. 2014, 10, 1741–1748, doi:10.3762/bjoc.10.181

• previously reported carbohydrate-based vaccine constructs [11] were prepared by a divergent approach, where the carbohydrate core was coupled to the resin-bound LCP adjuvanting moiety, followed by stepwise synthesis of the B cell epitopes using solid-phase peptide synthesis (SPPS). Using this divergent

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• ). Complete deprotection of 43 was accomplished in methanolic HCl to yield products 44 as mixtures of diastereoisomers. The Ugi reaction has been often used in solid-phase synthesis of compound libraries [83]. Suda et al. developed the optimal reaction conditions of the solid-phase Ugi reaction involving Rink

• (IC50 = 4.78 µM) was significantly lower than that of nikkomycin Z (IC50 = 0.06 µM). The remaining compounds 46 were inactive toward Candida albicans chitin synthase 2. Another approach to the solid-phase synthesis of nucleoside analogs was developed by Sun and Lee (Scheme 19) [85]. The library of 1344

• -nucleoside substrates, the ones dealing with the construction of a non-natural nucleobase predominated (18 examples). Interestingly, a combinatorial solid-phase approach has not been extensively exploited (2 examples). The findings concerning the syntheses of nucleoside antibiotic analogs or 1'-aza-analogs

Photoswitchable precision glycooligomers and their lectin binding

• Daniela Ponader,
• Sinaida Igde,
• Marko Wehle,
• Katharina Märker,
• Mark Santer,
• David Bléger and
• Laura Hartmann

Beilstein J. Org. Chem. 2014, 10, 1603–1612, doi:10.3762/bjoc.10.166

• & Bio-Systems, Research Campus Golm, 14424 Potsdam, Germany Humboldt University, Department of Chemistry, Brook-Taylor-Str. 2, 12489 Berlin, Germany 10.3762/bjoc.10.166 Abstract The synthesis of photoswitchable glycooligomers is presented by applying solid-phase polymer synthesis and functional

• the combination of solid phase polymer synthesis and tailor-made building blocks [7][8][9]. Through a stepwise assembly of our functional building blocks, we can now control the kind, number, and spacing of sugar ligands along a monodisperse scaffold. Thus, our precision glycomacromolecules allow for

• azobenzene functionalized with an Fmoc-protected aminomethyl group and a carboxylic acid both para to the N=N bond was used as one building block during solid-phase polymer synthesis of precision glycomacromolecules (see AZO, Figure 1) [19][20][21][22]. The benzylamine fragment was favored over the

Orthogonal dual thiol–chloroacetyl and thiol–ene couplings for the sequential one-pot assembly of heteroglycoclusters

• Michele Fiore,
• Gour Chand Daskhan,
• Baptiste Thomas and
• Olivier Renaudet

Beilstein J. Org. Chem. 2014, 10, 1557–1563, doi:10.3762/bjoc.10.160

• 3000+ Bruker Daltonics in positive mode. General procedure for solid-phase peptide synthesis. Assembly of all protected peptides was carried out on a synthesizer (Syro II, Biotage) using the Fmoc/t-Bu strategy and the Fmoc-Gly-SasrinTM resin. Coupling reactions were performed using, relative to 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

• precipitation of the complexes [30][31]. Alternatively, the application of surface plasmon resonance (SPR) also creates artificial situations not sufficiently related to the natural cellular events, thus requiring complex mathematical algorithms [32]. Most solid-phase immunoassays (ELLA, ELISA) also fall under

Bis(β-lactosyl)-[60]fullerene as novel class of glycolipids useful for the detection and the decontamination of biological toxins of the Ricinus communis family

• Hirofumi Dohi,
• Takeru Kanazawa,
• Akihiro Saito,
• Keita Sato,
• Hirotaka Uzawa,
• Yasuo Seto and
• Yoshihiro Nishida

Beilstein J. Org. Chem. 2014, 10, 1504–1512, doi:10.3762/bjoc.10.155

• undertook an alternative way by means of the SDS-PAGE. The results summarized in Table 1 show that the ricin protein was partitioned into two phases, i.e., solid phase (precipitates) and liquid phase (supernatants), after the sedimentation. Its distribution (%) in the solid phase increased with the

• multivalent protein–lactose interactions, prompted us to apply this glycolipid as a tool for the rapid detection and the decontamination of ricin and other biological toxins. By using an SDS-PAGE analysis, we successfully quantified distributions (%) of ricin in the aqueous and the solid phase. With this

Pyrene-modified PNAs: Stacking interactions and selective excimer emission in PNA₂DNA triplexes

• Alex Manicardi,
• Lucia Guidi,
• Alice Ghidini and
• Roberto Corradini

Beilstein J. Org. Chem. 2014, 10, 1495–1503, doi:10.3762/bjoc.10.154

• using standard Fmoc-based manual solid phase protocol. The crude products were purified by RP-HPLC and characterized by HPLC–UV–MS (Supporting Information File 1, Figures S6–S11). Thermal stability of PNA:DNA complexes The introduction of a modification in a PNA stand can lead to different effects

Design, automated synthesis and immunological evaluation of NOD2-ligand–antigen conjugates

• Marian M. J. H. P. Willems,
• Gijs G. Zom,
• Nico Meeuwenoord,
• Ferry A. Ossendorp,
• Herman S. Overkleeft,
• Gijsbert A. van der Marel,
• Jeroen D. C. Codée and
• Dmitri V. Filippov

Beilstein J. Org. Chem. 2014, 10, 1445–1453, doi:10.3762/bjoc.10.148

• incorporated SIINFEKL epitope on MHC-I molecules. However, stimulation of the NOD2 receptor in DCs was not sufficient to provide a strong immunostimulatory signal. Keywords: automated synthesis; glycopeptide; innate immunity; muramyl dipeptide; NOD2 receptor; solid phase synthesis; Introduction In recent

• . We here describe the assembly of MDP building blocks, suitable for automated solid phase peptide synthesis (SPPS), their use in the assembly of the four MDP-antigen conjugates 2–5 and the immunological evaluation of the constructs. Results and Discussion Synthesis of the conjugates The MDP-antigen

• conjugates 2–5 were prepared using an automated solid-phase peptide synthesis (SPPS) protocol. In all these syntheses commercially available Tentagel S RAM resin and amino acids were applied. The synthesis of the required MDP building blocks 10 and 16 is depicted in Scheme 1. The 3-azidopropanol spacer was

Biantennary oligoglycines and glyco-oligoglycines self-associating in aqueous medium

• Svetlana V. Tsygankova,
• Alexander A. Chinarev,
• Alexander B. Tuzikov,
• Nikolai Severin,
• Alexey A. Kalachev,
• Juergen P. Rabe,
• Alexandra S. Gambaryan and
• Nicolai V. Bovin

Beilstein J. Org. Chem. 2014, 10, 1372–1382, doi:10.3762/bjoc.10.140

• the structure PG II [12]. Spectra were recorded for the samples in solid phase. Model of the formation of tectomer layers by biantennary oligoglycines on a mica surface. The heights are given for Н-Gly4NH(СН2)10NHGly4-Н. Growth of the tectomer formed by the peptide Н-Gly4-NH(СН2)10-NHGly4-Н

Molecular recognition of surface-immobilized carbohydrates by a synthetic lectin

• Melanie Rauschenberg,
• Eva-Corrina Fritz,
• Christian Schulz,
• Tobias Kaufmann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 1354–1364, doi:10.3762/bjoc.10.138

• lectins on the immobilized carbohydrates provides insight into the affinity and selectivity of lectin–carbohydrate interaction. Results and Discussion The synthetic lectin HisHis was prepared by air oxidation of the tripeptide Cys-Hys-Cys (synthesized by solid phase peptide synthesis) as described

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

• their respective targets have led to tremendous progress for therapeutic applications in the last years. In order to increase the drugability of these frequently unstable and rapidly cleared molecules, chemical modifications are of great interest. Automated solid-phase peptide synthesis (SPPS) offers a

• : automated synthesis; automation; lipidation; PEGylation; peptide drugs; solid-phase peptide synthesis; therapeutic peptides; Introduction Peptides and proteins are involved in a large variety of biochemical processes and physiological functions. Peptides can consist of up to 50 amino acids and have

• intravenous) application, have prompted further research in this field [14]. Therefore, methods to prolong peptide stability are of great interest. Here, we highlight the importance of automated solid-phase peptide synthesis (SPPS) in the process of peptide modification. Principles of chemical synthesis of