Design, synthesis and photochemical properties of the first examples of iminosugar clusters based on fluorescent cores

• Mathieu L. Lepage,
• Antoine Mirloup,
• Manon Ripoll,
• Fabien Stauffert,
• Anne Bodlenner,
• Raymond Ziessel and
• Philippe Compain

Beilstein J. Org. Chem. 2015, 11, 659–667, doi:10.3762/bjoc.11.74

• adequate tailoring, including fluorescence amplification [50], and ratiometric pH reporter for imaging protein–dye conjugates in living cells [51], or display physiological binding of D-glucose [52]. The pyrene nucleus was also selected as an alternative fluorophore since it may be easily

Synthesis of multivalent carbohydrate mimetics with aminopolyol end groups and their evaluation as L-selectin inhibitors

• Joana Salta,
• Jens Dernedde and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2015, 11, 638–646, doi:10.3762/bjoc.11.72

• ; multivalency; selectins; sulfation; Introduction In a series of publications [1][2][3][4][5][6] our group reported on the syntheses of carbohydrate mimetics [7][8][9][10][11] that are based on aminopyrans, aminooxepanes or other aminopolyols. These compounds and their conjugates were prepared to be examined

• . Unfortunately, only a few of our prepared compounds were sufficiently soluble in water to be suitable for the SPR test. However, a series of other multivalent conjugates was synthesized by using click chemistry with the azide derived from aminopyran 1 and results will be published in due time [40]. Conclusion

Sequence-specific RNA cleavage by PNA conjugates of the metal-free artificial ribonuclease tris(2-aminobenzimidazole)

• Friederike Danneberg,
• Alice Ghidini,
• Plamena Dogandzhiyski,
• Elisabeth Kalden,
• Roger Strömberg and
• Michael W. Göbel

Beilstein J. Org. Chem. 2015, 11, 493–498, doi:10.3762/bjoc.11.55

• and Nutrition, Novum, SE-141 83 Huddinge, Sweden 10.3762/bjoc.11.55 Abstract Tris(2-aminobenzimidazole) conjugates with antisense oligonucleotides are effective site-specific RNA cleavers. Their mechanism of action is independent of metal ions. Here we investigate conjugates with peptide nucleic

• acids (PNA). RNA degradation occurs with similar rates and substrate specificities as in experiments with DNA conjugates we performed earlier. Although aggregation phenomena are observed in some cases, proper substrate recognition is not compromised. While our previous synthesis of 2-aminobenzimidazoles

• experiments [7]. PNA conjugates of both metal-containing and metal-free RNA cleavers have been effectively used as artificial nucleases towards different substrates [8][9][10][11]. Most notable is a copper-based PNAzyme which cleaves RNA site-specifically with substrate half-lifes as low as 30 minutes [12]. A

Synthesis and biological evaluation of a novel MUC1 glycopeptide conjugate vaccine candidate comprising a 4’-deoxy-4’-fluoro-Thomsen–Friedenreich epitope

• Manuel Johannes,
• Maximilian Reindl,
• Bastian Gerlitzki,
• Edgar Schmitt and
• Anja Hoffmann-Röder

Beilstein J. Org. Chem. 2015, 11, 155–161, doi:10.3762/bjoc.11.15

• antibodies elicited from this vaccine were found to cross-react with native TF epitopes of MCF-7 cancer cells. Similarly, Yang et al. found that fluorinated sTn antigen conjugates were significantly more immunogenic than their natural congeners and also elicited antibodies cross-reactive to sTn-positive LS-C

• epitopes. Use of tetanus toxoid (TTox) and bovine serum albumin (BSA) as immunogenic carrier proteins allows application of these conjugates in immunization studies and diagnostic ELISA experiments [44]. Results and Discussion Chemical synthesis of the 4’-fluoro-TF neo-glycoconjugate The synthesis of the 4

• toxoid (TTox) as carrier proteins in aqueous phosphate buffer at pH 9.5. Both 4’F-6TF-MUC1(20)-protein conjugates 18a/b were obtained after ultrafiltration using a 30 kDa membrane. MALDI–TOF mass spectrometry proved the antigen loading level of 18a to be on average seven molecules of glycopeptide per

Efficient deprotection of F-BODIPY derivatives: removal of BF₂ using Brønsted acids

• Mingfeng Yu,
• Joseph K.-H. Wong,
• Cyril Tang,
• Peter Turner,
• Matthew H. Todd and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2015, 11, 37–41, doi:10.3762/bjoc.11.6

• reacted respectively with the complementary propargyl-tri-Boc cyclam 12 [23][32] and 2-azidoethyl-tri-Boc cyclam 13 [24][25] under the modified click conditions we have reported previously [24] to generate the Boc-protected triazolyl-cyclam/F-BODIPY conjugates 3 and 4 in excellent yields. In attempting to

• structure determination is available as Supporting Information File 2 and is also available on request from the Cambridge Crystallographic Data Centre as deposition 1018518. Conversion of F-BODIPYs 1 to the parent dipyrrins 2. Synthesis of the triazolyl-cyclam/F-BODIPY conjugates 3 (A) and 4 (B). Reagents

Conjugates of methylated cyclodextrin derivatives and hydroxyethyl starch (HES): Synthesis, cytotoxicity and inclusion of anaesthetic actives

• Lisa Markenstein,
• Antje Appelt-Menzel,
• Marco Metzger and
• Gerhard Wenz

Beilstein J. Org. Chem. 2014, 10, 3087–3096, doi:10.3762/bjoc.10.325

• than the corresponding monomeric CD derivatives. Since the binding potentials of these CD conjugates were very high, they are promising candidates for new oral dosage forms of anaesthetic actives. Keywords: anaesthetics; complexation; cyclodextrin; LCST; lower critical solution temperature; midazolam

• protocol, introduced by Sharpless [31], using CuSO4 plus ascorbic acid as the catalyst already gave rise to high coupling yields. The resulting conjugates of HES and methylated CDs were isolated by ultrafiltration in nearly quantitative yields (Table 1). Nearly all propargyl groups at the HES detectable by

• conjugates, listed in Table 1, were clearly soluble in water at ambient conditions but most of them precipitated at elevated temperatures. This so-called lower critical solution temperature is typical for alkylated neutral polysaccharides and attributed to increasing hydrophobic interactions with increasing

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

• polypurine tract by reverse transcriptase [65]. In a series of N5-protonated urea-substituted bis-phenanthridinium derivatives (Scheme 22, general structure 9), the variation of the linker length connecting two urea-phenanthridinium conjugates significantly influenced the efficiency of intramolecular

• intercalator able to differentiate between A–U(T) and G–C base pairs by sign of opposite fluorimetric response. An introduction of the permanent positive charge by methylation of the heterocyclic nitrogen changed the binding mode of the conjugates with shorter linkers from minor groove binding to intercalation

• monomeric analogues) revealed significantly increased DNA-binding affinity and consequently enhanced telomerase and reverse transcriptase inhibition [69]. Conjugates of phenanthridine with other DNA and RNA active moieties Another common approach to increased selectivity of DNA- and RNA-targeting small

Detonation nanodiamonds biofunctionalization and immobilization to titanium alloy surfaces as first steps towards medical application

• Juliana P. L. Gonçalves,
• Afnan Q. Shaikh,
• Manuela Reitzig,
• Daria A. Kovalenko,
• Jan Michael,
• René Beutner,
• Gianaurelio Cuniberti,
• Dieter Scharnweber and
• Jörg Opitz

Beilstein J. Org. Chem. 2014, 10, 2765–2773, doi:10.3762/bjoc.10.293

• regioselective partial incorporation of biofunctional molecules into anodically grown oxide layers. The authors electrochemically immobilized nucleic acids on titanium alloys for its surface modification with bioactive molecules [21][22][23][24][25], as, e.g., oligonucleotides and RGD peptide conjugates, for

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

• Würzburg, Germany 10.3762/bjoc.10.288 Abstract Nanodiamonds functionalized with different organic moieties carrying terminal amino groups have been synthesized. These include conjugates generated by Diels–Alder reactions of ortho-quinodimethanes formed in situ from pyrazine and 5,6-dihydrocyclobuta[d

• conjugate [11]. We were able to show that the aromatic molecules immobilized by this technique can be further modified using conventional synthetic chemistry [12]. This enables the utilization of such diamond conjugates for biomedical applications as the C–C bound linker between the nanoparticle and the

• functionalization of nanodiamond with aromatic moieties carrying amino groups For the synthesis of a broad variety of aminated nanodiamond (ND) derivatives, a series of nanodiamond conjugates with different linker systems was synthesized starting from detonation nanodiamond 1 and thermally annealed nanodiamond 2 as

A small azide-modified thiazole-based reporter molecule for fluorescence and mass spectrometric detection

• Stefanie Wolfram,
• Hendryk Würfel,
• Stefanie H. Habenicht,
• Christine Lembke,
• Phillipp Richter,
• Eckhard Birckner,
• Rainer Beckert and
• Georg Pohnert

Beilstein J. Org. Chem. 2014, 10, 2470–2479, doi:10.3762/bjoc.10.258

• CuAAC with the azide-modified fluorophores. The rectangle represents the respective reporter unit. For clarity only reactions with the terminal lysine are depicted. Mass spectra of labeled L-lysine/DDY (10)/fluorophore conjugates 11 (containing BPT), 12 (containing DNS), 13 (containing NBD) and 14

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

• conjugates of saccharide–amino acids–nucleobase (SAN), like the previously reported conjugates of nucleobase–amino acids–saccharide (NAS) and nucleobase–saccharide–amino acids (NSA), are mammalian cell compatible. Keywords: cell compatibility; nucleobase; peptides; saccharide; Introduction As a result of

• evolution, nature selects saccharides, peptides, and nucleobases as the fundamental building blocks for the creation of biomacromolecules, which lay the molecular foundations of life. This simple fact and the self-assembly of small molecules in water have inspired us to explore the conjugates of those three

• types of building blocks for generating supramolecular nanofibers in water [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. Recently, we have demonstrated that not only the conjugates of nucleobase–amino acids–saccharide (NAS) [16][17][18] but also the conjugates of nucleobase–saccharide–amino acids

Synthesis and immunological evaluation of protein conjugates of Neisseria meningitidis X capsular polysaccharide fragments

• Laura Morelli,
• Damiano Cancogni,
• Marta Tontini,
• Alberto Nilo,
• Sara Filippini,
• Paolo Costantino,
• Maria Rosaria Romano,
• Francesco Berti,
• Roberto Adamo and
• Luigi Lay

Beilstein J. Org. Chem. 2014, 10, 2367–2376, doi:10.3762/bjoc.10.247

• by the in vitro bactericidal assay recently developed for the evaluation of MenX CPS conjugates [18]. Results and Discussion Improvements in α-H-phosphonate synthesis Our previous synthesis of oligomers 1–3 featured the use of 2-azido-2-deoxy glucopyranosyl building blocks and their corresponding

• synthesis of neo-glycoconjugates Fragments 1–3, obtained as previously reported [25], were employed as follows for the synthesis of the corresponding CRM197 conjugates. First the oligomers 1–3 were activated by reaction with an excess of SIDEA in the presence of triethylamine in DMSO (Scheme 3). The

• latter analytical technique enabled determination of the saccharide/protein molar ratio (saccharide loading). The characteristics of the prepared glycoconjugates are summarized in Table 1. A moderate loading (5–7 sugars/protein) was obtained in compounds 14–16 in respect to conjugates prepared by the

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

• of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Kraków, Poland 10.3762/bjoc.10.225 Abstract An investigation of the interactions of two novel and several known DBTAA–adenine conjugates with double-stranded DNA and RNA has revealed the DNA/RNA groove as the dominant binding site, which is

• in contrast to the majority of previously studied DBTAA analogues (DNA/RNA intercalators). Only DBTAA–propyladenine conjugates revealed the molecular recognition of AT-DNA by an ICD band pattern > 300 nm, whereas significant ICD bands did not appear for other ds-DNA/RNA. A structure–activity relation

• advantage of nucleobase incorporation in small molecule structures for the recognition of complementary nucleotides/polynucleotides [8][9][10]. Recent studies of the novel DBTAA-adenine conjugates AP3 and AP6 (Scheme 1) showed a highly selective binding of only AP3 to poly dT among all other ss-DNA/RNA, as

Synthesis of rigid p-terphenyl-linked carbohydrate mimetics

• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 1749–1758, doi:10.3762/bjoc.10.182

• conjugates may have even higher binding affinities and specificities than their flexible multivalent equivalents [14][15]. The rigidity of the system is supposed to improve the overall activity of the ligands by overcoming the entropic penalty of flexible multivalent scaffolds [16]. Cross-coupling reactions

• our group [24][25]. When they are coupled by amide bonds to gold nanoparticle and O-sulfated these conjugates gave extremely high binding affinities towards L- and P-selectin in sub-nanomolar concentrations. These results were achieved by a multivalent presentation (ca. 1000–1200 ligands per

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

• orthogonality of these two reactions for the growth of multifuncional dendrimers [22]. Results and Discussion Owing to their straightforward access, their high nucleophilicity and the stability of thioether conjugates, glycosyl thiols [23][24], α-D-ManSH 1 and β-D-GlcNAcSH 2 have been selected for this study

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

• × rs) can be calculated using the Stokes–Einstein equation and the viscosity of pure D2O (Table 1). As expected, nonavalent conjugates 12, 17, and 21 presented solvodynamic diameters in the range of roughly 3 nm when considering the decay of distinctive and common H-5 signals. These values remained

• ) with δ = 4 ms and Δ = 50 ms (Δ = 40 ms for 17 (circles)). Notably, such linear behavior was also obtained for the decay of the signal intensities of other protons located either in internal regions of the conjugates on aromatic or branching sections, or in the peripheral saccharidic belt (results not

• distributions for [M + 7H]7+ adduct. Determination of diffusion data and solvodynamic diameters of nonavalent conjugates 12, 17, and 21 by diffusion NMR experiments. Supporting Information Supporting Information File 524: Experimental procedures, characterization data, NMR, IR and mass spectra and NMR

Postsynthetic functionalization of glycodendrons at the focal point

• Thisbe K. Lindhorst and
• Katharina Elsner

Beilstein J. Org. Chem. 2014, 10, 1482–1487, doi:10.3762/bjoc.10.152

• of compounds, the carbohydrates. Carbohydrates are involved in numerous biological recognition processes, where they are often displayed in the form of multivalent conjugates such as on the surface of cells [1]. To investigate multivalency in carbohydrate recognition, multivalent glycomimetics, for

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 antigen. Here we describe the design, automated synthesis and immunological evaluation of a set of four muramyl dipeptide–peptide antigen conjugates. Muramyl dipeptide (MDP) represents a well-known ligand for the intracellular NOD2 receptor and our study shows that covalently linking an MDP-moiety

• years the study of pattern recognition receptors (PRRs) and associated ligands has evolved tremendously [1]. The discovery of Toll-like receptors (TLRs) [2] in the late 1990s has had a major impact on the field of immunology. This is reflected in the exploration of conjugates consisting of a PRR-ligand

• that conjugates, in which Pam3CSK4 or CpG DNA were incorporated, showed an increased uptake of conjugated peptide. Increased DC maturation and enhanced antigen presentation was achieved in comparison to the mixture of the single peptide and ligands [13][14]. In the late 1990s the cytosolic nucleotide

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

• -carbohydrates, in particular multiarm PEGylation, is presented. Keywords: bioavailability; carbohydrates; conjugates; glycoPEGylation; multivalent glycosystems; multivalent PEGylation; Introduction In recent years, the modification of biotherapeutics by covalent conjugation with polyethyleneglycol (PEG) known

• the molecule to be conjugated, maintaining its biological activity. Examples of activated PEGs are shown in Figure 2. Multiarm PEGs have the advantage of presenting several sites for conjugation and, in the higher MW conjugates, the arms are far away enough from each other to allow independent

• ]. Mannose was also PEGylated in order to target drugs specifically to mannose receptors present in liver endothelial cells. Mannosyl PEGylated polyethylenimine (PEI) conjugates were synthesized either by direct coupling the mannose and the PEG chain to the PEI backbone (Figure 3A) or by attaching the

Synthesis of the first examples of iminosugar clusters based on cyclopeptoid cores

• Mathieu L. Lepage,
• Alessandra Meli,
• Anne Bodlenner,
• Céline Tarnus,
• Francesco De Riccardis,
• Irene Izzo and
• Philippe Compain

Beilstein J. Org. Chem. 2014, 10, 1406–1412, doi:10.3762/bjoc.10.144

• a valency-corrected basis) [3][7]. The modest inhibition enhancements observed with DNJ-cyclopeptoid conjugates 10 could thus be due to the high flexibility of their amide backbone [14][15][16][17]. Conclusion In conclusion, we have reported the efficient synthesis of the first examples of

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

• glycine residues for the derivatives with core C10 and six residues for core C2 failed due to their low solubility and, consequently, the impossibility of separating them from the intermediates of the synthesis. Sialo conjugates of biantennary oligoglycines were obtained from the corresponding diamines

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

• and polymers offers a virtually unlimited number of encodings. In nature, carbohydrates are often linked to lipids, peptides or proteins. These conjugates are found inside cells, on cell membranes as well as in extracellular fluids and matrices. Surprisingly, the general understanding of the function

• , Man, see Figure 1) were selected for the fabrication of carbohydrate arrays. To provide carbohydrate inks suitable for microcontact printing (µCP), NANA was conjugated via its C1 carboxylic acid moiety, whereas the other carbohydrates were conjugates as β-glycosides (Glc, Gal) and α-glycosides (Man

Glycosystems in nanotechnology: Gold glyconanoparticles as carrier for anti-HIV prodrugs

• Fabrizio Chiodo,
• Marco Marradi,
• Javier Calvo,
• Eloisa Yuste and
• Soledad Penadés

Beilstein J. Org. Chem. 2014, 10, 1339–1346, doi:10.3762/bjoc.10.136

• were incubated with 0.1 equivalents of ABC or 3TC conjugate with respect to the glucose conjugates on the GNP. This amount allowed the insertion of ~10% of the thiol-ending drugs. After precipitation and washings with EtOH, the GNPs were dissolved in a 90:10 mixture of water/DMSO to ensure a better

• paragraph). The ester derivatives were not detected in the EtOH washings after the GNPs precipitation (by MALDI–MS and 1H NMR) indicating that practically all the drug conjugates were linked on the gold surface. Drug quantification and release of the drug from GNPs We studied the stability of the GNPs

Design and synthesis of multivalent neoglycoconjugates by click conjugations

• Feiqing Ding,
• Li Ji,
• Ronny William,
• Hua Chai and
• Xue-Wei Liu

Beilstein J. Org. Chem. 2014, 10, 1325–1332, doi:10.3762/bjoc.10.134

• approach to multivalent 3-tosylamino-2,3-dideoxyneoglyco conjugates 4 with potential biochemical applications involving click conjugations as the key reaction step (Figure 3). Results and Discussion Primarily, we successfully synthesized propargyl 3-p-toluenesulfonamido-4,6-di-O-acetyl-2,3-dideoxy-α-D

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

• , demonstrating a prolonged action profile of the acylated conjugates. Thus, the extended action was proposed to be facilitated by serum albumin binding, which leads to gradual peptide release and an prolonged circulation time [91]. Since then, many biological relevant peptides and proteins were chemically

• peptides: Another elegant way to modulate pharmacokinetic and -dynamic properties of peptide drugs is the formation of drug–polymer conjugates by PEGylation. PEGylation is the covalent modification of peptides with methoxy polyethyleneglycol polymer units of an averaged molecular weight. PEG itself is

• during SPPS allowing EPR (electron paramagnetic resonance) studies to investigate conformational changes during receptor binding [129]. Here, synthesis on solid support could be easily realized. Nevertheless, conditions for cleavage of the peptide conjugates from the resin had to be optimized owing to