Synthesis of cyclic N¹-pentylinosine phosphate, a new structurally reduced cADPR analogue with calcium-mobilizing activity on PC12 cells

• Ahmed Mahal,
• Stefano D’Errico,
• Nicola Borbone,
• Brunella Pinto,
• Agnese Secondo,
• Valeria Costantino,
• Valentina Tedeschi,
• Giorgia Oliviero,
• Vincenzo Piccialli and
• Gennaro Piccialli

Beilstein J. Org. Chem. 2015, 11, 2689–2695, doi:10.3762/bjoc.11.289

• ]. Among these NNs there is the cyclic ADP-ribose (cADPR 1, Figure 1), a metabolite strictly involved in the homeostasis of cellular calcium ions. cADPR is a second messenger that activates the ryanodine receptors of the sarcoplasmic reticulum and mobilizes Ca2+ ions in many cell types of protozoa, plants

Smart molecules for imaging, sensing and health (SMITH)

• Bradley D. Smith

Beilstein J. Org. Chem. 2015, 11, 2540–2548, doi:10.3762/bjoc.11.274

• imaging, ion-pair receptors, rotaxane synthesis, squaraine rotaxanes, and synthtavidin technology. The article concludes with a short perspective of likely future directions in biomedical supramolecular chemistry. Keywords: fluorescence; ion-pair receptors; membrane transport; molecular imaging; rotaxane

• on the cell surface during the process of apoptosis or programmed cell death. Thus, phosphatidylserine is an excellent biomarker of cell death and an attractive target for molecular imaging. We reasoned that synthetic anion receptors such as zinc dipicolylamine (ZnDPA) coordination complexes would

• ][21][22]. The latest discovery is a set of molecular ZnDPA probes that selectively target parasite infections in living subjects such as Leishmaniasis, a lethal disease that afflicts many millions of people around the world [23]. Ion-pair receptors Our early experience with membrane transport raised

Syntheses of 2-substituted 1-amino-4-bromoanthraquinones (bromaminic acid analogues) – precursors for dyes and drugs

• Enas M. Malik,
• Younis Baqi and
• Christa E. Müller

Beilstein J. Org. Chem. 2015, 11, 2326–2333, doi:10.3762/bjoc.11.253

• proposed the compound to interact with ATP-binding sites [33], and it was subsequently used as a pharmacological tool for studying ATP and other nucleotide receptors. RB-2 has played a crucial role in identifying different purine receptor subtypes, since it was found to selectively block only certain

Cu(I)-catalyzed N,N’-diarylation of natural diamines and polyamines with aryl iodides

• Svetlana P. Panchenko,
• Alexei D. Averin,
• Maksim V. Anokhin,
• Olga A. Maloshitskaya and
• Irina P. Beletskaya

Beilstein J. Org. Chem. 2015, 11, 2297–2305, doi:10.3762/bjoc.11.250

• receptors and antileishmanial activity [15][16][17]. Up to date no general non-catalytic approach to N,N’-diarylpolyamines has yet been described. Synthetic procedures are multistep [17][18] though sometimes they can be performed as one-pot syntheses [19]. Several catalytic approaches have been described in

Cholesterol lowering effects of mono-lactose-appended β-cyclodextrin in Niemann–Pick type C disease-like HepG2 cells

• Keiichi Motoyama,
• Yumi Hirai,
• Rena Nishiyama,
• Yuki Maeda,
• Taishi Higashi,
• Yoichi Ishitsuka,
• Yuki Kondo,
• Tetsumi Irie,
• Takumi Era and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2015, 11, 2079–2086, doi:10.3762/bjoc.11.224

• concentrations within the cells but also minimum concentration at non-target cells, thereby amalgamating high treatment efficacy with low side effects. Of various receptors, asialoglycoprotein receptors (ASGPR) expressing in abundance on hepatocytes could provide advantages for hepatocyte-selective delivery [11

Supramolecular chemistry: from aromatic foldamers to solution-phase supramolecular organic frameworks

• Zhan-Ting Li

Beilstein J. Org. Chem. 2015, 11, 2057–2071, doi:10.3762/bjoc.11.222

• structures was to explore their potential functions as acyclic receptors. Moore et al. had utilized this approach to investigate the binding of m-phenylene ethynylene foldamers for nonpolar organic molecules in polar media [44]. All the C=O oxygen atoms of 21 point into the cavity of the helix, which has a

• molecules to evaluate their binding to these triazole foldamers. He finally found that these foldamers were good halogen bonding receptors for tritopic and ditopic guests, including 30 in dichloromethane or its mixture with hydrocarbons. Yanhua further utilized the C–H····F hydrogen bonding to induce the

Synthesis of constrained analogues of tryptophan

• Elisabetta Rossi,
• Valentina Pirovano,
• Marco Negrato,
• Giorgio Abbiati and
• Monica Dell’Acqua

Beilstein J. Org. Chem. 2015, 11, 1997–2006, doi:10.3762/bjoc.11.216

• to the identification of new dual NK1/NK2 antagonists [12], as shown in Figure 2 (B). In 2003, the pharmaceutical company Zentaris patented a series of tetrahydrocarbazole derivatives as ligands for G-protein-coupled receptors (GPCR), and in particular as antagonists of the gonadotropin-releasing

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

• Mohamed Ramadan El Sayed Aly,
• Hosam Ali Saad and
• Shams Hashim Abdel-Hafez

Beilstein J. Org. Chem. 2015, 11, 1922–1932, doi:10.3762/bjoc.11.208

• regulator of cellular cholesterol [8]. Synthetic BODIPY–cholesterol conjugates were reported as probes for visualization of intracellular cholesterol pools and for monitoring cholesterol efflux from cells to extracellular receptors [9]. ABCA1 plays an inevitable role in the resistance against tumorgenesis

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• the reaction of 256 with catalyst 5 in the presence of vinyl acetate (258) (Scheme 53). The RRM approach is useful to design diverse analogs of the marine toxin dysiherbaine, which displays antagonistic activity on ionotropic glutamate receptors from oxanorbornenes [54]. The report reveals the

Tetrathiafulvalene-based azine ligands for anion and metal cation coordination

• Awatef Ayadi,
• Aziz El Alamy,
• Olivier Alévêque,
• Magali Allain,
• Nabil Zouari,
• Mohammed Bouachrine and
• Abdelkrim El-Ghayoury

Beilstein J. Org. Chem. 2015, 11, 1379–1391, doi:10.3762/bjoc.11.149

• -responsive receptors for neutral and/or charged guest sensing applications have been prepared [18][19][20][21][22]. On this ground, chemosensors capable of recognizing anionic and/or cationic species constitute an important area of increasing research in supramolecular chemistry, considering the ubiquitous

Donor–acceptor type co-crystals of arylthio-substituted tetrathiafulvalenes and fullerenes

• Xiaofeng Lu,
• Jibin Sun,
• Shangxi Zhang,
• Longfei Ma,
• Lei Liu,
• Hui Qi,
• Yongliang Shao and
• Xiangfeng Shao

Beilstein J. Org. Chem. 2015, 11, 1043–1051, doi:10.3762/bjoc.11.117

• ratio of the co-crystals, this work further demonstrates that Ar-S-TTFs are promising candidates to serve as receptors for fullerenes and have diverse supramolecular structures. Crystal structures The single crystalline structure of the complex is suitable for X-ray single crystal diffraction

• -crystal. The present results suggest that Ar-S-TTF molecules would be promising receptors for fullerenes as they are easily accessible. Meanwhile, Ar-S-TTFs possess the unique structural features to encapsulate fullerenes. That means the size matches with that of fullerenes and the flexibility is helpful

Glycoluril–tetrathiafulvalene molecular clips: on the influence of electronic and spatial properties for binding neutral accepting guests

• Yoann Cotelle,
• Marie Hardouin-Lerouge,
• Stéphanie Legoupy,
• Olivier Alévêque,
• Eric Levillain and
• Piétrick Hudhomme

Beilstein J. Org. Chem. 2015, 11, 1023–1036, doi:10.3762/bjoc.11.115

• molecular receptors prone to specifically recognize neutral molecules through donor–accceptor interactions are of particular interest [12], the unique π-donating ability and the planar geometry of the TTF building-block are suited to the construction of such receptors. Nevertheless, the incorporation of TTF

• as a π-donating element in molecular clips or tweezers for recognition of neutral electron acceptor guests is still relatively unexplored [13]. Molecular clips and tweezers can be defined as receptors presenting an open cavity composed of two interaction sites which are separated by a spacer [13][14

• , glycoluril-based molecular clips have shown that they were capable of acting as excellent receptors by exploiting the distance between the two aromatic sidewalls which is usually close to 7 Å. Since then, a large number of host systems based on this principle have been synthesized in order to use them for

Tuning of tetrathiafulvalene properties: versatile synthesis of N-arylated monopyrrolotetrathiafulvalenes via Ullmann-type coupling reactions

• Vladimir A. Azov,
• Diana Janott,
• Dirk Schlüter and
• Matthias Zeller

Beilstein J. Org. Chem. 2015, 11, 860–868, doi:10.3762/bjoc.11.96

• . Although being reported in the literature, it has so far not found wide spread use and was employed only with a narrow scope of aromatic derivatives with electron-donating substituents and alkylthio-substituted (R = SAlkyl) MPTTFS. Being interested in the preparation of calix[4]arene receptors with MPTTF

Peptide–polymer ligands for a tandem WW-domain, an adaptive multivalent protein–protein interaction: lessons on the thermodynamic fitness of flexible ligands

• Katharina Koschek,
• Vedat Durmaz,
• Oxana Krylova,
• Marek Wieczorek,
• Shilpi Gupta,
• Martin Richter,
• Alexander Bujotzek,
• Christina Fischer,
• Rainer Haag,
• Christian Freund,
• Marcus Weber and
• Jörg Rademann

Beilstein J. Org. Chem. 2015, 11, 837–847, doi:10.3762/bjoc.11.93

• ; proline-rich peptide sequences; Introduction Multivalency is a general principle in nature for increasing the affinity and specificity of ligand–receptor interactions [1]. Multivalent binding is characterized by the cooperative, over-additive enhancement of binding affinities of ligands and receptors in

• a defined spatial arrangement. The strongest affinity enhancement can be expected in the case of a perfectly fitting, rigid arrangement of ligands and receptors (Figure 1A). In such cases the affinity of the multivalent ligand can be potentiated by the degree of multivalency. Prominent examples for

• this perfect fit have been reported reaching an exponential binding increase [2]. Rigid scaffolds can be used to present ligands in defined spatial arrangements and thus can be exploited to investigate the distances between receptor sites as “molecular ruler” [3][4]. Many multivalent receptors in

Influence of length and flexibility of spacers on the binding affinity of divalent ligands

• Susanne Liese and
• Roland R. Netz

Beilstein J. Org. Chem. 2015, 11, 804–816, doi:10.3762/bjoc.11.90

• receptors [1]. Each multivalent ligand consists of several monovalent ligands that are connected via a scaffold. The binding affinity of such a multivalent ligand is determined by the interplay between gain in binding energy and loss of entropy associated with conformational degrees of freedom. The more

• therefore desirable to derive a model that allows one to predict the binding affinity of a given ligand-scaffold construct. Several theoretical studies have been dedicated to study the interaction between multi- and polyvalent ligands with receptors arranged on planar surfaces [8][9][10][11][12][13]. The

• constant Kmono of a monovalent ligand interacting with a monovalent receptor is defined as with [L] and [R] being the concentration of unbound ligands and unbound receptors and [RL] the concentration of bound ligands or equivalently the concentration of bound receptors. If half of all receptors are

Orthogonal dual-modification of proteins for the engineering of multivalent protein scaffolds

• Michaela Mühlberg,
• Michael G. Hoesl,
• Christian Kuehne,
• Jens Dernedde,
• Nediljko Budisa and
• Christian P. R. Hackenberger

Beilstein J. Org. Chem. 2015, 11, 784–791, doi:10.3762/bjoc.11.88

• , to engineer precise protein models and study a variety of multivalent receptors. Experimental General protocol for glycol cleavage and oxime ligation on TTL. A solution of the TTL (12 µM; 100 mM phosphate buffer, 100 mM NaCl, pH 7) was mixed with NaIO4 (3 equiv) and shaken for 1 h at 15 °C. N-Acetyl

Regulation of integrin and growth factor signaling in biomaterials for osteodifferentiation

• Qiang Wei,
• Theresa L. M. Pohl,
• Anja Seckinger,
• Joachim P. Spatz and
• Elisabetta A. Cavalcanti-Adam

Beilstein J. Org. Chem. 2015, 11, 773–783, doi:10.3762/bjoc.11.87

• important regulators for the direct or indirect modulation of cell behavior [4]. Cells interact with the ECM via several kinds of transmembrane receptors, in which the major class involved is integrin’s [5]. Integrin ligands in the ECM include fibronectin, vitronectin, collagen, and laminin, which contain

• stable gradients of growth factors to regulate their bioavailability [11]. This matrix-immobilization of the factors might result in long-term binding to cell surface receptors, since the binding affinity of ECM-factors is relatively weak compared to growth factor receptor interactions [8]. Moreover, the

• differentiation. It has been shown that integrins exert an extensive crosstalk with many growth factor receptors [16]. Integrin ligands actively participate in the regulation of growth factor-mediated signaling. Ligand–integrin interactions can induce ligand-independent partial activation of growth factor

Glycodendrimers: tools to explore multivalent galectin-1 interactions

• Jonathan M. Cousin and
• Mary J. Cloninger

Beilstein J. Org. Chem. 2015, 11, 739–747, doi:10.3762/bjoc.11.84

• glycoconjugates to mediate biological activity [10][11][12][13][14][15][16]. Specifically, galectin-1 has been reported to be involved in multivalent mechanisms that cluster cell surface glycoproteins [10][17], cross-link receptors [13][18], and form lattices and larger aggregates [12][19][20]. Synthetic

• of glycoconjugates (TF antigen Mucin-1) on adjacent cells which directly facilitates aggregation; and (ii) clustering of receptors (TF antigen Mucin-1) which exposes adhesion molecules that interact with adhesion molecules on neighboring cells to cause aggregation. All four generations of the

Probing multivalency in ligand–receptor-mediated adhesion of soft, biomimetic interfaces

• Stephan Schmidt,
• Hanqing Wang,
• Daniel Pussak,
• Simone Mosca and
• Laura Hartmann

Beilstein J. Org. Chem. 2015, 11, 720–729, doi:10.3762/bjoc.11.82

• protein receptors are formed to control cell–cell recognition, cell adhesion and related processes. The aim of this work is to shed light on the principles of complex formation between surface anchored carbohydrates and receptor surfaces by measuring the specific adhesion between surface bound mannose on

• carbohydrates of the glycocalyx, a glycan coating enveloping prokaryotic or eukaryotic cells. By specific binding to cell receptors, the carbohydrate units of the glycocalyx control important processes such as cell adhesion, communication and inflammatory response [1]. For this reason great effort is set forth

• ligands are typically oligomers consisting of multiple subunits of varying complexity. When binding to receptors this leads to a receptor clustering or so-called glycocluster effect. However, multivalency even goes further: For example when cells form contact layers of surface anchored carbohydrates 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

• addition, HA is able to interact with three major classes of cell surface receptors, namely CD44 (cluster of differentiation 44), RHAMM (receptor for HA-mediated motility) and ICAM-1 (intracellular adhesion molecule-1) [10][11]. CD44 is a heterogeneous, transmembrane glycoprotein which is overexpressed on

Potential of acylated peptides to target the influenza A virus

• Daniel Lauster,
• Damian Pawolski,
• Julian Storm,
• Kai Ludwig,
• Rudolf Volkmer,
• Henry Memczak,
• Andreas Herrmann and
• Sumati Bhatia

Beilstein J. Org. Chem. 2015, 11, 589–595, doi:10.3762/bjoc.11.65

• mediated by a multivalent interaction between HA binding pockets and cell surface receptors as a monovalent interaction is too weak for stable binding [10][11]. Peptide-based self-assembled nanostructures can be used as the simplest platform for the multivalent display of ligands, although this approach

Synthesis and chemosensing properties of cinnoline-containing poly(arylene ethynylene)s

• Natalia A. Danilkina,
• Petr S. Vlasov,
• Semen M. Vodianik,
• Andrey A. Kruchinin,
• Yuri G. Vlasov and
• Irina A. Balova

Beilstein J. Org. Chem. 2015, 11, 373–384, doi:10.3762/bjoc.11.43

• by the nature of the polymer backbone, e.g., polyphenylenes, polythiophenes, poly(phenylene vinylene)s, poly(phenylene ethynylene)s etc, or by their chemosensing properties [3][4]. The latter depends on the nature of receptors (recognizing units) incorporated into a polymer chain that bind an analyte

Stereoselective cathodic synthesis of 8-substituted (1R,3R,4S)-menthylamines

• Carolin Edinger,
• Jörn Kulisch and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2015, 11, 294–301, doi:10.3762/bjoc.11.34

• applications reported so far, are the uses as building blocks in supramolecular receptors [29][30][31][32][33][34] or the synthesis of high-performance stationary phases for liquid chromatography [35][36][37][38]. (−)-Menthone (2) can be converted to menthylamine by different methods: A general way to convert

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• , various therapies targeted at interfering with this process were investigated [6]. The favored clinical targets are the VEGF receptors, which have led to the development and approval of monoclonal antibodies against VEGF and VEGF receptor tyrosine kinase inhibitors [3]. However, the existing therapy

• through inhibiting of tumor-cell proliferation, migration and induction of apoptosis. In addition, it is a dual inhibitor of the phosphorylation of VEGF and PDGF receptors, thus interrupting the angiogenetic processes required for tumor growth [30]. Recently, it was reported that its anti-angiogenesis

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

• ; Introduction A re-occurring principle of nature to mediate or increase biological activity is dimerization [1]. Many protein receptors dimerize upon activation and recruit their active form by this transformation. This process is mainly initiated by dimeric natural products or symmetric bivalent ligands, which