Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

• based on the ability of CDs to extract lipids from the cell membrane. The objective of this contribution is to focus on the potential use of natural and chemically modified CDs in the vast array of medical and biological applications. Review Cyclodextrins: synthesis, structure and physicochemical

• . For sake of clarity, only some typical applications of CD/cellular interactions are reported. i) Cell membrane cholesterol efflux As previously mentioned, CDs are able to interact and to complex cholesterol and others lipids [114]. A great number of publications deals with this topic and with the

Tunable microwave-assisted method for the solvent-free and catalyst-free peracetylation of natural products

• Manuela Oliverio,
• Paola Costanzo,
• Monica Nardi,
• Carla Calandruccio,
• Raffaele Salerno and
• Antonio Procopio

Beilstein J. Org. Chem. 2016, 12, 2222–2233, doi:10.3762/bjoc.12.214

• molecules to pass the cell membrane [5] and, once inside the cells, acetyl groups can be removed by intracellular esterases thus resulting in an augmented dose of active principle [2][3]. Moreover, peracetylation affects the pharmacokinetics by prolonging the half-life of the unprotected molecules whose

Synthesis and NMR studies of malonyl-linked glycoconjugates of N-(2-aminoethyl)glycine. Building blocks for the construction of combinatorial glycopeptide libraries

• Markus Nörrlinger,
• Sven Hafner and
• Thomas Ziegler

Beilstein J. Org. Chem. 2016, 12, 1939–1948, doi:10.3762/bjoc.12.183

• animal and many bacterial cells. It is covalently bound to the surface of the cell membrane through glycoproteins and plays a major role in numerous biologically important recognition mechanisms like cell–cell recognition, signal transduction and immunological processes [1][2][3][4]. Therefore

New synthetic strategies for xanthene-dye-appended cyclodextrins

• Milo Malanga,
• Andras Darcsi,
• Mihaly Balint,
• Gabor Benkovics,
• Tamas Sohajda and
• Szabolcs Beni

Beilstein J. Org. Chem. 2016, 12, 537–548, doi:10.3762/bjoc.12.53

• fluorophores for labeling in order to assess if these versatile molecules cross biological barriers (e.g., cell membrane, blood–brain barrier) and to follow their distribution in living matter [3]. Among the fluorescent dyes, the group of fluorophores based on xanthene scaffolds is one of the most popular. Two

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

• results indicate that 3 and 4 possess almost the same activity, thus indicating that the role of the pyrophosphate bridge is not stringent and that the introduction of an alkyl chain in the N1 position of the purine base improves the permeation of the cell membrane by passive diffusion or through an

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

• selectively recognize the anionic head group of phosphatidylserine [12]. Furthermore, binding strength is amplified by electrostatic attraction of the cationic receptor to the apoptotic cell membrane with a negative surface potential. We developed a family of fluorescent ZnDPA probes for fluorescence

• , and I apologize for any distortion of credit. To assist the interested reader, each research topic includes references to relevant review articles by leading groups in the field. Membrane transport Molecular transporters that alter the concentration gradients of anions and biomolecules across a cell

• membrane have various biological effects as reagents for cell biology research and as potential pharmaceuticals [3][4]. In the early 1990’s, most of the supramolecular research on facilitated membrane transport using carrier molecules focused on metal cation transport. As a young professor, with an

Biocatalysis for the application of CO₂ as a chemical feedstock

• Apostolos Alissandratos and
• Christopher J. Easton

Beilstein J. Org. Chem. 2015, 11, 2370–2387, doi:10.3762/bjoc.11.259

• each case, as for any multi-enzymatic synthesis, will depend on a combination of factors such as the number of enzymes to be utilised, the ease of substrate and product diffusion through the cell membrane, and the presence of unwanted background reactions. Within a well-understood cellular chassis, the

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

• coupled both Arg and His groups in different ratios to dPG-NH2 via the latter strategy (Scheme 1). By introducing Arg on the dendritic scaffold, this group can serve as a complexing agent and the surplus guanidium groups with high affinity to phosphate groups can interact with the cell membrane and

• interactions of these polymers with the cell membrane and depends on multiple factors such as molecular weight, the nature of the polymer surface, and its charge density [30]. The results of the in vitro MTT assays on the NIH 3T3 cell line for cytotoxicity evaluation of AAdPG polyplexes are shown in Figure 3

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

• vivo situation. Typically, such antiviral compounds will be applied intravenously or by inhalation to allow a systemic distribution or a tissue specific targeting within the infected host. However, in those cases amphiphilic peptides are in an environment of cell membrane surfaces being in excess to

• hemagglutination by acylated antiviral peptides was drastically reduced in the presence of additional membranes (here liposomes). Taken into consideration that the in vivo situation is characterized by an excess of cell membrane surfaces serving as targets for the amphiphilic peptides, the multivalent presentation

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

• the corresponding aglycone. The aglycone passes through the cell membrane by passive diffusion and undergoes phase-II metabolism in enterocytes and the liver, leading to glucuronides as the main metabolites. However, a release of the aglycones from the glucuronides in tissues or cells with β

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

• attributed to the surface charge of the coating material chitosan. CS coated cationic NCs exhibited a stronger affinity for the negatively charged cell membrane [44]. CS can increase the chance of cellular uptake of nanoparticles by improving the residence time at the cellular surface due to the

• electrostatic interaction between the cell membrane and nanoparticle since positively charged CS has the ability to interact with the negatively charged surface membrane of cells via electrostatic forces [45]. The permeation of CPT both in solution form and in nanocapsule formulations across a Caco-2 cell

• 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

Effects of RAMEA-complexed polyunsaturated fatty acids on the response of human dendritic cells to inflammatory signals

• Éva Rajnavölgyi,
• Renáta Laczik,
• Viktor Kun,
• Lajos Szente and
• Éva Fenyvesi

Beilstein J. Org. Chem. 2014, 10, 3152–3160, doi:10.3762/bjoc.10.332

• acids are not produced by mammals, although they are essential for hormone synthesis and maintenance of cell membrane structure and integrity. They have recently been shown to inhibit inflammatory reactions and also emerged as potential treatment options for inflammatory diseases, such as rheumatoid

• ). The use of RAMEA for enhancing aqueous solubility of n−3 fatty acids has the unambiguous advantage over applying RAMEB (the β-cyclodextrin analog), since there is no interaction with cell membrane cholesterol. In vitro differentiated moDC were left untreated or were stimulated by bacterial

• mediated through the GP120 receptor without interfering with the cell membrane structure. Keywords: cell membrane; cell surface markers; cyclodextrin; enzyme immunoassay; flow cytometry; monocyte-derived dendritic cells; proinflammatory cytokines; RAMEA; solubilization; Introduction The n−3

A study on the inhibitory mechanism for cholesterol absorption by α-cyclodextrin administration

• Takahiro Furune,
• Naoko Ikuta,
• Yoshiyuki Ishida,
• Hinako Okamoto,
• Daisuke Nakata,
• Keiji Terao and
• Norihiro Sakamoto

Beilstein J. Org. Chem. 2014, 10, 2827–2835, doi:10.3762/bjoc.10.300

• ][25]. Conversely, it has been reported that α-CD releases lecithin from the cell membrane [26][27][28][29][30]. In this study, we investigated the effect of α-CD on the mixed micelles (bile salt micelles) using Fed-State Simulated Intestinal Fluid (FeSSIF) [31] and the effect of α-CD on the micellar

• -CD released lecithin from the cell membrane [26][27][28][29][30], this is the first time that the effect of α-CD on lecithin precipitation from bile salt micelles has been described. The taurocholate content in the filtrate was unaffected by the α-CD addition (Figure 2B). Because α-CD has a low

Encapsulation of biocides by cyclodextrins: toward synergistic effects against pathogens

• Véronique Nardello-Rataj and
• Loïc Leclercq

Beilstein J. Org. Chem. 2014, 10, 2603–2622, doi:10.3762/bjoc.10.273

• of the complexes by observing the morphology of E. coli. When butylparaben or triclosan were used as biocidal agent in the presence of CP-β-CD, the cell membrane was not affected by the complex suggesting that the biocide/CP-β-CD complexes inhibit only the metabolism. Indeed, triclosan exhibits its

• polymers which tend to cause cell membrane lysis (see below the amphiphilic biocides section). The authors concluded that the cationic groups on the CP-β-CD facilitate the biocides approach onto the negatively charged cell membrane improving accordingly the antimicrobial activity of the biocides. In 2014

• amphiphilic biocides mechanism is based on four-steps: (a) the biocide diffuses in the solution, (b) electrostatic interactions maintained the charged biocides in the vicinity of the cell membrane, (c) the biocide is inserted between the phospholipids of the cell membrane, and (d) the modification of the

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

• exploration [26]. As an amino acid, Phe or naphthAla increases molecular aromatic–aromatic interactions [19][21][27]. Arg-Gly-Asp, which is a well-established tripeptidic epitope, that modulates mammalian cell adhesion through binding with integrins on the cell membrane [28][29]. Thymine or adenine, as a

Synthesis of isoprenoid bisphosphonate ethers through C–P bond formations: Potential inhibitors of geranylgeranyl diphosphate synthase

• Xiang Zhou,
• Jacqueline E. Reilly,
• Kathleen A. Loerch,
• Raymond J. Hohl and
• David F. Wiemer

Beilstein J. Org. Chem. 2014, 10, 1645–1650, doi:10.3762/bjoc.10.171

• blot analyses of K562 cells (a human-derived, myeloid leukemia cell line) treated with this compound make clear that it penetrates the cell membrane at a concentration sufficient to impact GGPP levels. For example in the presence of micromolar DGBP, Rap1a which is normally found to be fully

The myxocoumarins A and B from Stigmatella aurantiaca strain MYX-030

• Tobias A. M. Gulder,
• Snežana Neff,
• Traugott Schüz,
• Tammo Winkler,
• René Gees and
• Bettina Böhlendorf

Beilstein J. Org. Chem. 2013, 9, 2579–2585, doi:10.3762/bjoc.9.293

• with cell membrane stability [21]. Inhibition of acetyl-CoA carboxylase is exerted by soraphen A1α (2), which has been shown to be a potent and broad spectrum fungicide [22][23]. The most dominant target of myxobacterial antifungal agents, however, is the mitochondrial respiratory chain [21]. The

Synthesis and antibacterial activity of monocyclic 3-carboxamide tetramic acids

• Yong-Chul Jeong and
• Mark G. Moloney

Beilstein J. Org. Chem. 2013, 9, 1899–1906, doi:10.3762/bjoc.9.224

• (rel-PSA < 15.0%, c log P > 1.77 and c log D (7.4) > 0.41) might make penetration of the bacterial cell membrane more difficult. However, 3-carboxamides 2c–g and 3a–d, all possessing alkyl substituents, including a benzyl group on the amide function, are also active to Gram-positive strains

Synthesis and physicochemical characterization of novel phenotypic probes targeting the nuclear factor-kappa B signaling pathway

• Paul M. Hershberger,
• Satyamaheshwar Peddibhotla,
• E. Hampton Sessions,
• Daniela B. Divlianska,
• Ricardo G. Correa,
• Anthony B. Pinkerton,
• John C. Reed and
• Gregory P. Roth

Beilstein J. Org. Chem. 2013, 9, 900–907, doi:10.3762/bjoc.9.103

• validation using a panel of known receptor and kinase-based counter screens [7]. Because activation of NF-κB is known to be initiated through protein kinase C (PKC), we hypothesized that selectivity could be possible by the fact that PKC activation occurs downstream from cell membrane antigen and growth

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

• series of biotinylated analogues of the purine scaffold Hsp90 inhibitor PU-H71 (1a) and its desisopropyl analogue 1b. The goal of this study was to optimize probe 2a [9] and develop analogues capable of efficiently permeating the cancer cell membrane so that they may be used as tools to investigate

A peptidic hydrogel that may behave as a “Trojan Horse”

• Nicola Castellucci,
• Giorgio Sartor,
• Natalia Calonghi,
• Carola Parolin,
• Giuseppe Falini and
• Claudia Tomasini

Beilstein J. Org. Chem. 2013, 9, 417–424, doi:10.3762/bjoc.9.44

• drugs, which should be sufficiently polar for ease of administration and successful distribution in the organism, but also adequately hydrophobic so as to traverse the lipid bilayer of the cell membrane. Because they do not fulfill these physical properties, a large number of drug leads fail to make it

• the cell membrane surface than does the β-sheet conformation [5]. Low-molecular-weight hydrogelators (LMWHGs) are defined as small molecules that self-assemble into long fibers, resulting in the formation of a gel [6][7][8][9][10]. Recently, several examples of peptide or peptidomimetic gelators have

Mannose-decorated cyclodextrin vesicles: The interplay of multivalency and surface density in lectin–carbohydrate recognition

• Ulrike Kauscher and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2012, 8, 1543–1551, doi:10.3762/bjoc.8.175

• guest 2 is far below 50%. The low rate of agglutination could be a consequence of a slow rearrangement of the glycocalyx, i.e., a “receptor-induced clustering” of mannose in the presence of ConA. Conclusion In this study we described a biomimetic model for the glycocalyx of a cell membrane based on

Binaphthyl-anchored antibacterial tripeptide derivatives with hydrophobic C-terminal amino acid variations

• John B. Bremner,
• Paul A. Keller,
• Stephen G. Pyne,
• Mark J. Robertson,
• K. Sakthivel,
• Kittiya Somphol,
• Dean Baylis,
• Jonathan A. Coates,
• John Deadman,
• Dharshini Jeevarajah and
• David I. Rhodes

Beilstein J. Org. Chem. 2012, 8, 1265–1270, doi:10.3762/bjoc.8.142

• on compounds of type 1 (Figure 1) and related cyclic systems implicated the possibility of more than one mode of action [8]. As noted for other cationic peptide derivatives [9][10][11][12], cell membrane damage could well be one of these actions, together with some more specific interactions. Dual

• -action type behaviour has been shown for the vancomycin analogue telavancin, which affects cell wall synthesis and the integrity of the cell membrane [13]. Conclusion In conclusion, seven novel binaphthyl-anchored tripeptide derivatives have been prepared and tested for antibacterial activity against S

Design of a novel tryptophan-rich membrane-active antimicrobial peptide from the membrane-proximal region of the HIV glycoprotein, gp41

• Evan F. Haney,
• Leonard T. Nguyen,
• David J. Schibli and
• Hans J. Vogel

Beilstein J. Org. Chem. 2012, 8, 1172–1184, doi:10.3762/bjoc.8.130

• the gp41 protein is of particular interest, because it contains five Trp residues, is believed to bind at the surface of the viral membrane [11] and plays an important role in fusing the viral membrane to the target cell membrane. The solution structure of the 19-residue peptide (gp41w) bound to

Synthetic glycopeptides and glycoproteins with applications in biological research

• Ulrika Westerlind

Beilstein J. Org. Chem. 2012, 8, 804–818, doi:10.3762/bjoc.8.90

• the discovery, by Springer et al., that glycoproteins on the outer cell membrane of epithelial tumor cells have an altered glycosylation consisting of the Thomsen-Friedenreich (T-) antigen and its precursor TN-antigen structure, the synthesis and evaluation of anti-tumor vaccines have been a topic of