Multivalent dendritic polyglycerolamine with arginine and histidine end groups for efficient siRNA transfection

• Fatemeh Sheikhi Mehrabadi,
• Hanxiang Zeng,
• Mark Johnson,
• Cathleen Schlesener,
• Zhibin Guan and
• Rainer Haag

Beilstein J. Org. Chem. 2015, 11, 763–772, doi:10.3762/bjoc.11.86

• on dPG (Mn = 8.4 kDa, PDI = 1.7) were converted to amino groups according to an earlier published procedure (Scheme S1, Supporting Information File 1) [27]. The high density of amines on dPG facilitates the introduction of groups like amino acids by feasible strategies like amide coupling. Here, we

• according to a published procedure [33]. Fifty percent of all (~110) hydroxy groups on dendritic polyglycerol were functionalized with amino groups in a three-step protocol [27]. Briefly, the transformation was started with the mesylation of the hydroxy groups on dPG. In the next step, the mesylated

• in specific molar ratios. 1.2 Equivalents of BOP and DIPEA with respect to the amino groups were added to the reaction subsequently. The reaction mixture was stirred at room temperature overnight. This mixture was then transferred directly into a dialysis tube of 1000 MWCO and dialyzed in methanol

Exploring monovalent and multivalent peptides for the inhibition of FBP21-tWW

• Lisa Maria Henning,
• Sumati Bhatia,
• Miriam Bertazzon,
• Michaela Marczynke,
• Oliver Seitz,
• Rudolf Volkmer,
• Rainer Haag and
• Christian Freund

Beilstein J. Org. Chem. 2015, 11, 701–706, doi:10.3762/bjoc.11.80

• according to the published procedure [19] (see Figures S2 and S3 in Supporting Information File 1 for GPC and MALDI–TOF–MS analysis of the hPG-OH core). Seventy percent of all hydroxy groups (≈120 OH groups) on hPG-OH were functionalized with amino groups in a three-step protocol as reported in the

Synthesis of a hexasaccharide partial sequence of hyaluronan for click chemistry and more

• Marina Bantzi,
• Stephan Rigol and
• Athanassios Giannis

Beilstein J. Org. Chem. 2015, 11, 604–607, doi:10.3762/bjoc.11.67

• reducing conditions (Zn, AcOH) [28] and subsequently the liberated amino groups were acetylated to furnish compound 8. Eventually, the silyl group and all benzylidene moieties were removed by treatment with Olah's reagent to give, after acetylation, derivative 9. Finally, oxidation of the terminal olefinic

3-Glucosylated 5-amino-1,2,4-oxadiazoles: synthesis and evaluation as glycogen phosphorylase inhibitors

• Marion Donnier-Maréchal,
• David Goyard,
• Vincent Folliard,
• Tibor Docsa,
• Pal Gergely,
• Jean-Pierre Praly and
• Sébastien Vidal

Beilstein J. Org. Chem. 2015, 11, 499–503, doi:10.3762/bjoc.11.56

• functionality between the 1,3,4-oxadiazole core and glucose [26] (I) or aromatic [27] (J) groups was recently investigated (Figure 1). The present study reports on the introduction of such amino groups between the oxadiazole and aromatic cores. Two synthetic strategies were used to obtain such scaffolds based

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

• Tor E. Kristensen

Beilstein J. Org. Chem. 2015, 11, 446–468, doi:10.3762/bjoc.11.51

• conventional mindset, embracing acidic, instead of alkaline acylation conditions, a potentially nimble and direct conversion of unprotected hydroxyamino acids into their corresponding side-chain esters, in a single step, can be envisaged. In a suitable acidic medium, amino groups will be prevented from

The reactions of 2-ethoxymethylidene-3-oxo esters and their analogues with 5-aminotetrazole as a way to novel azaheterocycles

• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess and
• Viktor I. Saloutin

Beilstein J. Org. Chem. 2015, 11, 385–391, doi:10.3762/bjoc.11.44

• to conclude that the molecule of compound 11 is symmetric and bears one methine proton, two amino groups and two ethoxycarbonyl substituents. The final structure of compound 11 as 5-[2,6-diamino-3,5-bis(ethoxycarbonyl)pyridinium-1-yl]tetrazol-1-ide was confirmed by X-ray diffraction (Figure 2). The

Formulation development, stability and anticancer efficacy of core-shell cyclodextrin nanocapsules for oral chemotherapy with camptothecin

• Hale Ünal,
• Naile Öztürk and
• Erem Bilensoy

Beilstein J. Org. Chem. 2015, 11, 204–212, doi:10.3762/bjoc.11.22

• based on its amino groups. Coating with CS resulted in an increment in particle size due to the adsorption of CS molecules on the nanocapsule surface [34]. This coating is believed to be of importance due to the penetration enhancing properties of chitosan through the intestinal mucosa by opening of

• to higher cellular adhesion and increasing residence time at the cell surface provided by CS molecules. This finding suggests that with chitosan-coated cationic NCs, electrostatic interactions between positively charged CS amino groups and the negatively charged cell membrane occurred. Therefore, the

Redox active dendronized polystyrenes equipped with peripheral triarylamines

• Toshiki Nokami,
• Naoki Musya,
• Tatsuya Morofuji,
• Keiji Takeda,
• Masahiro Takumi,
• Akihiro Shimizu and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2014, 10, 3097–3103, doi:10.3762/bjoc.10.326

• examined before studying the functionalization of dendronized polystyrene. Thus, di(p-methoxyphenyl)amino groups were introduced to 4 using a Buchwald–Hartwig amination [11]. The choice of a base is crucial for this transformation, and the transformation was successfully carried out using Cs2CO3 as a base

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

• fluorescent labeling was realized in three steps: 1) building in azido moieties, 2) transforming the azido groups into amino groups and 3) coupling the proper fluorescent compound to the amino groups. The other strategy started by functionalization of the monomer prior to the branching. Either the fluorescent

• the impurities level. The strategy that was built-up for achieving the labeling can introduce some undesired alteration into the polymeric structure. If the target is a strictly homogeneously fluorescent-labeled β-CD polymer, then the presence of unreacted amino groups, owing to an incomplete

• fluorescent labeling, could be an undesired modification of the starting material that can affect some properties such as the water solubility and/or ionizability. Furthermore, the quantification of these (eventual) residual amino groups would be troublesome. The strategy that was applied to overcome the

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

• modulation of its amino groups at 3 and 8 positions of the phenanthridine ring [52][53]. Systematic changing of the ethidium bromide exocyclic amines into guanidine, pyrrole, urea, and various substituted ureas revealed importance of electron-donor properties of substituents at the 3- and 8-position of the

• phenanthridinium relative to the unmodified primary amino groups. Namely, derivatives of EB having substituents with weaker electron-donor properties exhibited a stronger fluorescence emission than EB, while a stronger electron-donating substituent exhibited a much lower fluorescence emission. Such behaviour could

• quenching [54][55]. Taking into account the research results of several other groups, a general rule could be drawn that phenanthridines with no amino groups yield strong fluorescence in water but emission is totally quenched by DNA binding; one amino group at (usually) position 8 results in only a small

A novel 4-aminoantipyrine-Pd(II) complex catalyzes Suzuki–Miyaura cross-coupling reactions of aryl halides

• Claudia A. Contreras-Celedón,
• Darío Mendoza-Rayo,
• José A. Rincón-Medina and
• Luis Chacón-García

Beilstein J. Org. Chem. 2014, 10, 2821–2826, doi:10.3762/bjoc.10.299

• tolerant for both electron-donating and electron-withdrawing substituents; our protocol successfully accommodated the free hydroxy and amino groups as substituents on the aryl iodides and bromides without additional protection procedures, and the reactions with these substrates produced the corresponding

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

• as control to verify the interaction of amino groups and the titanium based alloy. Furthermore, products 3 and 6 can be seen as ‘inversely modified’ DND with a terminal phosphate and a secondary amide 3 or with a primary amine and a secondary phosphoroamidate 6. This might help to assess the

• (1000 cm−1) in 4 and 5 and amino groups around 950 cm−1 and 1560 cm−1 in 4, 5 and 6. It is still possible to see some carboxylic groups on 4, which may result from an incomplete oxidation process. A positive signal of the integration of the phosphate group can be seen in 3 and 6, at the wavenumber of

• by hydrogen bridging and electrostatic affinity to positively charged amino groups. SEM results Figure 4 from unfunctionalized DND demonstrate a better interaction with the titanium oxide layer than carboxylated DND with O-PEA 3 and silanized DND 5. This may be explained by the presence of several

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

• ]pyrimidine derivatives. For the quantification of primary amino groups a modified photometric assay based on the Kaiser test has been developed and validated for different types of aminated nanodiamond. The results correspond well to values obtained by thermogravimetry. The method represents an alternative

• wet-chemical quantification method in cases where other techniques like elemental analysis fail due to unfavourable combustion behaviour of the analyte or other impediments. Keywords: amino groups; carbon nanomaterials; Diels–Alder reaction; Kaiser test; nanodiamond; pyrazine; Introduction Surface

Linear-g-hyperbranched and cyclodextrin-based amphiphilic block copolymer as a multifunctional nanocarrier

• Yamei Zhao,
• Wei Tian,
• Guang Yang and
• Xiaodong Fan

Beilstein J. Org. Chem. 2014, 10, 2696–2703, doi:10.3762/bjoc.10.284

• chain of two PHEMA blocks via a pseudo-one-step hydrosilylation reaction. Finally, modified β-CD monomers were bonded to the amino groups of PDMAEMA block side chain by the action of ionic bonds (P3). The P3 self-assembled into stable micelles with a core–shell structure in aqueous solution. The

• groups of HBPCSi (Supporting Information File 1, Figures S6 and S7). Next, P3 was synthesized by the quaternization reaction of the amino groups of the PDMAEMA block side chain with monoiodide-substituted β-CD (mono-6-I-β-CD) (Supporting Information File 1, Scheme S3). The corresponding reaction

• [23][24]. Thus, the positive charge of the current polymers should be ascribed to the presence of the PDMAEMA segments carrying tertiary amino groups. Therefore, when P1, P2 and P3 self-assembled into the micelles in aqueous solution, the PDMAEMA segments formed the outer shell of micelles, leading to

A versatile δ-aminolevulinic acid (ΑLA)-cyclodextrin bimodal conjugate-prodrug for PDT applications with the help of intracellular chemistry

• Chrysie Aggelidou,
• Theodossis A. Theodossiou,
• Antonio Ricardo Gonçalves,
• Mariza Lampropoulou and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 2414–2420, doi:10.3762/bjoc.10.251

• wide β-CD opening available for inclusion of a hydrophobic guest molecule for intracellular transport, (ii) positively charged secondary and primary amino groups at physiological pH thus able to interact with negatively charged components of the cell membranes and achieve cell penetration [11] and (iii

• of hydrolysable ester bonds with 1. The resulting conjugate 2 (Scheme 1), expected to be water soluble, comprises seven secondary and multiple primary (maximum seven) amino groups in the final form. Initial attempts to directly couple compound 1 with the terminal hydroxy groups in 4 consistently

• amino groups is expected to play a major role in the interaction with the anionic parts of phospholipids, rather than the β-CD cavity and its encapsulation ability of hydrophobic membrane components. Conclusion The present work demonstrates the synthesis and characterization of the bimodal conjugate

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

• . In this way, almost quantitative recovery of the activated sugars 11–13 was achieved. Active esters 11–13 were then coupled with the amino groups of the protein in sodium phosphate buffer (100 mM NaPi, pH 7.2) at room temperature for 24 h (Scheme 3). The glycoconjugates 14–16 were purified from 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

• ]). Namely, parameters such as the groove width and depth, steric obstructions like the amino groups of guanine, H-bonding patterns, as well as polynucleotide charge density and the curvature of the ds-helix backbone all differ significantly across the double stranded examples mentioned above (Table S1

• case of GC-DNA this is due to the steric hindrance of the guanine amino groups inside the groove. In the case of the AU-RNA, it is because of the very wide and shallow shape, which does not support the binding of a small molecule (Table S1, Supporting Information File 1). This is consistent with the

Proton transfers in the Strecker reaction revealed by DFT calculations

• Shinichi Yamabe,
• Guixiang Zeng,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2014, 10, 1765–1774, doi:10.3762/bjoc.10.184

• )-CNH+ R-CH(NH2)-CNH+ + OH2 → R-CH(NH2)-C(OH)=NH + H+ However, the proton affinity (PA) of the nitrile is much smaller than that of the amino group, for example, the PAs of the cyano and amino groups of 2-amino-propanonitrile (Me-CH(NH2)-CN) are 190.7 and 199.6 kcal/mol, respectively. Thus, in the

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

• overall yields of 6% or 13% are quite respectable. The distance between the two terminal amino groups is in the range of 2.0 nm (according to optimized molecular geometry obtained by MM2 calculations performed by ChemBio3D Ultra 11.0 from ChemBioOffice 2008). Conclusion We successfully established methods

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

• of novel polyzwitterions based on cellulose carbamate with carboxylic- and primary amino groups is discussed. Starting from cellulose carbonate, the fully protected zwitterion is efficiently synthesized that could be converted into the polyanion, polycation, and polyzwitterion via the orthogonal

• , the falling point of inflection between the pKa values has to be considered. In Figure 4 the maximum of dpH/dV at 285 μL indicates an IP of 7.3. Naturally, the summation of the charges of the functional groups has to yield a neutral molecule at the IP and a ratio of carboxylic groups to amino groups

• pH value of 5 and 8.5, the turbidity and the Z-average diameter increase significantly. In the pH scale from 4.5 to 6, the zeta potential decreases from +25 to +5 mV due to the deprotonation of the carboxylic moiety. In alkaline solution the zeta potential increases with decreasing pH and the amino

Why a diaminopyrrolic tripodal receptor binds mannosides in acetonitrile but not in water?

• Diogo Vila-Viçosa,
• Oscar Francesconi and
• Miguel Machuqueiro

Beilstein J. Org. Chem. 2014, 10, 1513–1523, doi:10.3762/bjoc.10.156

• . In the case of the first generation amino groups, they are much closer to each other, with limited conformational freedom, resulting in much lower pKa values. The small number of titrable sites in the receptor allows us to analyze in detail the population of each possible microstate. In particular

• group). From Figure 3, we observe that, in general, the position of protons (positive charges) is such that repulsion is minimized. For example, with two protons, the preferred state is the one with two second generation amino groups protonated which allows the two charges to be more distant to each

• microstates with the second generation amino groups protonated are preferred and the ones with protons in different arms are also significantly populated. In these states, there are two microstates that are almost not populated due to the high repulsion when protonating two groups in the same arm or in the

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

• adenovirus coat for vaccine development [5], antibodies or antibody fragments to prolong their circulating half-lives in vivo [6] and selective alkylation and acylation of amino groups in a somatostatin analog using two different PEG reagents [7]. Also, PEGylation of low molecular weight drugs in order to

• amino groups of chitosan favor interaction with negatively charged cellular surfaces. The amino groups of chitosan may be derivatized with PEG chains, thus modifying the physicochemical properties. Chitosan was first modified in the amino group of the glucosamine units with a PEG-aldehyde to yield an

• imine (Schiff base), which was subsequently reduced to PEG-g-chitosan with sodium cyanoborohydride [55], allowing retention of net charge. PEGylation can also be accomplished by condensation of the free amino groups with activated PEGs, such as PEG-NHS or PEG-p-nitrophenyl carbonate, converting the

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

• ’ principle, i.e., by their C-termini, so that the two amino groups are terminal. The obtained compounds differ threefold. Firstly, they differ by core X nature: hydrophilic oligoethylene glycol (OEG), hydrophobic flexible decamethylene (C10), or short ethylene (C2). Secondly, the length of oligoglycine

• scattering method (DLS). We found that the ability of association depends on the number of the glycine units in the antennae, the nature of the core, the pH, and the peptide concentration. It is known that the charge of terminal amino groups of the protonated form of oligoglycines hinders association. To

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

• ]. Since then, the chemistry and application of this innovative drug delivery system has been developed crucially. Currently, there are many strategies to incorporate PEG into peptides. They can be attached to amino groups by acylation or alkylation, to thiols, hydroxy or amide groups [108]. These polymers

• automated SPPS have to be reconsidered. If a lysine side chain is modified, the Nvoc group will have to be used to protect the N-terminus and the lysine side chains that are important for the biological functions of the peptide. After cleavage of the peptide from the resin, only the desired amino groups are

Solid-phase-supported synthesis of morpholinoglycine oligonucleotide mimics

• Tatyana V. Abramova,
• Sergey S. Belov,
• Yulia V. Tarasenko and
• Vladimir N. Silnikov

Beilstein J. Org. Chem. 2014, 10, 1151–1158, doi:10.3762/bjoc.10.115

• -containing residue to the morpholine nitrogen in monomers 5a,d,e resulted in the appearance of duplicate signals of the nucleobases and morpholine protons in the NMR spectra (see Experimental) similar to morpholinooxalyl nucleosides [8]. After completion of the loading, the unreacted amino groups were capped