Synthesis of novel sulfide-based cyclic peptidomimetic analogues to solonamides

• José Brango-Vanegas,
• Luan A. Martinho,
• Lucinda J. Bessa,
• Andreanne G. Vasconcelos,
• Alexandra Plácido,
• Alex L. Pereira,
• José R. S. A. Leite and
• Angelo H. L. Machado

Beilstein J. Org. Chem. 2019, 15, 2544–2551, doi:10.3762/bjoc.15.247

• . Cyclic thioether peptides have been found in the chemical skeletons of natural products and synthetic ones that display a wide variety of activities, including antibiotics [31], vascular cell adhesion molecule-1 antagonists [32] and anticardiolipin antibodies [33][34]. Two MBH adducts (2) (R = Me, heptyl

Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

• Rosana Ribić,
• Ranko Stojković,
• Lidija Milković,
• Mariastefania Antica,
• Marko Cigler and
• Srđanka Tomić

Beilstein J. Org. Chem. 2019, 15, 1805–1814, doi:10.3762/bjoc.15.174

• and IgG1, respectively. Therefore, isotype profile of antigen specific anti-OVA IgG antibodies, IgG1 and IgG2a, is usually measured as a marker of the Th1 and Th2 type immune response bias [40][41]. In this study, the type of generated immune response was indirectly estimated by quantification of OVA

• -specific IgG1 (for activation of Th2 type) and IgG2a (for activation of Th1 type) and calculation of the respective IgG1/IgG2a ratio. When the amount of anti-OVA IgG1 antibodies was measured (Figure 5a), it was observed that in all groups high levels of IgG1 antibody was present and the highest response

• , which was also statistically significant (p < 0.001), was given by compound 21. A slight suppression was noticed only in the production of anti-OVA IgG1 antibodies when compound 16 was administered. A statistically significant enhancement in anti-OVA IgG2a production (Figure 5b) was observed in groups

A chemically contiguous hapten approach for a heroin–fentanyl vaccine

• Yoshihiro Natori,
• Candy S. Hwang,
• Lucy Lin,
• Lauren C. Smith,
• Bin Zhou and
• Kim D. Janda

Beilstein J. Org. Chem. 2019, 15, 1020–1031, doi:10.3762/bjoc.15.100

• States has necessitated the development of new strategies to treat addiction. Monoclonal antibodies and antidrug vaccines provide a tool that both aids addiction management and reduces the potential for overdose. Dual drug vaccines formulated by successive conjugation or by mixture have certain drawbacks

• not limited to, new non-addictive opioid drugs, innovative treatments to prevent relapse, and preventing and/or reversing overdose. Monoclonal antibodies and antidrug vaccines are immunopharmacological treatments that address two of these highlighted needs: addiction management and a potential for

• reducing overdose. By chemically attaching a non-immunogenic drug-like molecule to an immunogenic carrier protein, a vaccine is formed that has the capacity to stimulate an immune response, generating antibodies capable of binding the targeted drug. Moreover, when a user consumes the drug, the antibodies

Lectins of Mycobacterium tuberculosis – rarely studied proteins

• Katharina Kolbe,
• Sri Kumar Veleti,
• Norbert Reiling and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2019, 15, 1–15, doi:10.3762/bjoc.15.1

• found to contain molecules immunologically related to mycotin on their cell surface [73]. Furthermore, adhesion of Mtb to mouse peritoneal macrophages was inhibited using antimycotin antibodies, which led to the assumption that mycotin-like molecules are involved in the interaction of Mtb with

• Streptomyces olivaceoviridis) [77][78]. This secreted protein was crystallized in 2010 by Patra et al., however, a three-dimensional structure has yet to be resolved [79]. Recently Nogueira et al. detected high titers of IgG antibodies against sMTL-13 in sera from TB patients, a response found to be diminished

• following successful antituberculosis therapy [80]. The results underline that mycobacterial lectins are expressed in vivo and might be important for Mtb infections. Furthermore, anti-sMTL-13 antibodies could serve as a biomarker of disease treatment progression. The exact function of sMTL-13 and its ligand

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• . Numerous inhibitors have been developed against AB toxins, targeting toxin transcription, assembly, receptor binding and enzyme function [51]. A set of antibodies against diverse toxins has recently been approved for therapeutic use, which demonstrates the scientific and medical feasibility of entering the

• the extracellular environment through a needle-like structure into a host cell. The blockade of toxin secretion or needle assembly has been an active area of research, and small molecules as well as antibodies are currently being developed [30][66][67]. The TTSS needle tip protein PcrV was found to be

Impact of Pseudomonas aeruginosa quorum sensing signaling molecules on adhesion and inflammatory markers in endothelial cells

• Carmen Curutiu,
• Florin Iordache,
• Veronica Lazar,
• Aurelia Magdalena Pisoschi,
• Aneta Pop,
• Mariana Carmen Chifiriuc and
• Alina Maria Hoban

Beilstein J. Org. Chem. 2018, 14, 2580–2588, doi:10.3762/bjoc.14.235

• and anti-CD28 antibodies. PQS does not affect cell viability while OdDHL inhibits cell proliferation and viability [20]. In addition, OdDHL inhibits the release of IL-2 and TNFα while PQS stimulates the release of these cytokines [21]. OdDHL can control PQS production, demonstrating that both

• -conjugated (FITC - fluorescein-isothiocyanate and PE - phycoerythrin) primary antibodies against IL-1β, IL-6, ICAM-1 PECAM-1, P-selectin, VE-cadherin (Beckman-Coulter). Endothelial cells were detached using trypsin (Sigma-Aldrich, USA) and washed in PBS. Cells were then incubated with the primary antibodies

• at room temperature in the dark for 30 min. Further, the cells were washed twice and centrifuged at 400g, 10 min, in PBS suplemented with 1% BSA. For negative controls, endothelial cells were stained with the corresponding isotype-matched IgG antibodies (Beckman-Coulter). Flow cytometry data were

Synthetic avenues towards a tetrasaccharide related to Streptococcus pneumonia of serotype 6A

• Aritra Chaudhury,
• Mana Mohan Mukherjee and
• Rina Ghosh

Beilstein J. Org. Chem. 2018, 14, 1095–1102, doi:10.3762/bjoc.14.95

• antibodies elicited by SPn 6A would be effective against SPn 6B as well [10][11][12][13]. But recent studies have shown that serotype specific immune responses are elicited by the antibodies and that they cross react slowly [14]. As a result the importance of the presence of the capsular polysaccharide of

A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine

• Bettina Riedl and
• Walther Schmid

Beilstein J. Org. Chem. 2018, 14, 856–860, doi:10.3762/bjoc.14.71

• , glycoproteins serve as ligands for specific extracellular recognition processes toward, e.g., enzymes, lectins or antibodies [2]. In O-linked glycoproteins, also known as mucins, GalNAc becomes covalently α-linked to serine or threonine during post-translational modifications [3][4][5]. This glycoconjugate

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

BODIPY-based fluorescent liposomes with sesquiterpene lactone trilobolide

• Ludmila Škorpilová,
• Silvie Rimpelová,
• Michal Jurášek,
• Miloš Buděšínský,
• Jana Lokajová,
• Roman Effenberg,
• Petr Slepička,
• Tomáš Ruml,
• Eva Kmoníčková,
• Pavel B. Drašar and
• Zdeněk Wimmer

Beilstein J. Org. Chem. 2017, 13, 1316–1324, doi:10.3762/bjoc.13.128

• . Specific drug targeting can be achieved by using, for example, antibodies, peptides, polyethylene glycol polymers, and last but not least, liposomes, which have been nowadays extensively investigated [1][2]. In general, liposomes are employed in order to enhance the therapeutic index of an applied drug by

Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience

• Serge Pérez and
• Daniele de Sanctis

Beilstein J. Org. Chem. 2017, 13, 1145–1167, doi:10.3762/bjoc.13.114

• of the families of most glycan-interacting proteins (including glycosyl transferases and hydrolases, lectins, antibodies and GAG-binding proteins) are presented. Examples concerned with glycolipids and colloids are also covered as well as some dealing with the structures and multiscale architectures

• of polysaccharides. Insights into the kinetics of catalytic events observed in the crystalline state are also presented as well as some aspects of structure determination of protein in solution. Keywords: antibodies; carbohydrate binding domains; cellulose; glycosaminoglycans; glycolipids; glycosyl

• modifications. Transporters and proteins purely involved in recognition (lectin, antibodies, carbohydrate binding modules, glycosaminoglycan binding proteins) are the other important classes of carbohydrate-binding proteins. Figure 7 shows the evolution of the number of carbohydrate interacting proteins that

G-Protein coupled receptors: answers from simulations

• Timothy Clark

Beilstein J. Org. Chem. 2017, 13, 1071–1078, doi:10.3762/bjoc.13.106

• stable enough for crystallization. The solution to this problem has been to use the variable domains of camelid antibodies, which are generally designated protein nanobodies, as a surrogate for the G-protein [18]. This technique will be discussed in the context of the simulations below. Note, however

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• designing an ELISA approach to detect anti-carbohydrate antibodies. The innovative procedure exploited the use of very small AuNPs (2 nm) coated with tetrasaccharide epitopes of HIV gp120 or tetrasaccharide epitopes of Streptococcus pneumoniae Pn14PS. The GAuNPs so obtained were directly coated on

• commercial ELISA plates and anti-carbohydrate antibodies were detected in the nanomolar range both using purified anti-HIV human monoclonal antibodies or serum from immunized mice against S. pneumoniae. Detection of carbohydrate–influenza virus interactions The SERS methodology was extended to the

• -based approach, which aim to trigger the production of specific and functional antibodies that prevent initial infection limiting pathogen/viral dissemination. Recent publications suggest that many different aspects are becoming clear and have to be underlined. The design of anti HIV-1 vaccines depends

Expression, purification and structural analysis of functional GABA transporter 1 using the baculovirus expression system

• Jing Hu,
• Chris Weise,
• Christoph Böttcher,
• Hua Fan and
• Jian Yin

Beilstein J. Org. Chem. 2017, 13, 874–882, doi:10.3762/bjoc.13.88

• (GFP) fusion protein was functionally expressed in insect Sf9 cells by the BAC-TO-BAC® baculovirus expression system. A two-step procedure to purify the GAT1/GFP fusion protein from insect Sf9 cells has been established and involves immunoaffinity chromatography using self-prepared anti-GFP antibodies

• functions of GAT1 [27], could be purified in a functional form. In addition, the GFP tag has several advantages for further work. For example, it provides a powerful means for affinity purification with specific anti-GFP antibodies that have already been produced, generates green fluorescence for the

• antibodies and other impurities from the eluates of the immunoaffinity column. The elution profile of the GAT1/GFP protein is shown in Figure 4A. Compared with the standard proteins (Figure 4B), two main peaks (1 and 2) appear, corresponding to Mr of 320 and 162 kDa, respectively. The fractions (300 μL per

Total synthesis of a Streptococcus pneumoniae serotype 12F CPS repeating unit hexasaccharide

• Peter H. Seeberger,
• Claney L. Pereira and
• Subramanian Govindan

Beilstein J. Org. Chem. 2017, 13, 164–173, doi:10.3762/bjoc.13.19

• Deutschland GmbH, Magnusstrasse 11, 12489 Berlin, Germany 10.3762/bjoc.13.19 Abstract The Gram-positive bacterium Streptococcus pneumoniae causes severe disease globally. Vaccines that prevent S. pneumoniae infections induce antibodies against epitopes within the bacterial capsular polysaccharide (CPS). A

• antibodies that serve as tools for vaccine design [19] and for the detection of pathogenic bacteria such as Bacillus anthracis [20][21]. S. pneumoniae 12F CPS consists of hexasaccharide repeating units containing the [→4)-α-L-FucpNAc-(1→3)-β-D-GalpNAc-(1→4)-β-D-ManpNAcA-(1→] polysaccharide backbone with a

Benzothiadiazole oligoene fatty acids: fluorescent dyes with large Stokes shifts

• Lukas J. Patalag and
• Daniel B. Werz

Beilstein J. Org. Chem. 2016, 12, 2739–2747, doi:10.3762/bjoc.12.270

• methods are commonly employed. Either unnatural fluorescent dyes are inserted into the membrane (e.g., pyrene) or the hydrophilic part of lipids is utilized for the covalent attachment of fluorophores. Another possibility is the use of fluorescently labelled antibodies which bind membrane components such

Synthesis, dynamic NMR characterization and XRD studies of novel N,N’-substituted piperazines for bioorthogonal labeling

• Constantin Mamat,
• Marc Pretze,
• Matthew Gott and
• Martin Köckerling

Beilstein J. Org. Chem. 2016, 12, 2478–2489, doi:10.3762/bjoc.12.242

• , proteins or antibodies [34][35], mild and fast methods for radiolabeling are mandatory because of the short half-live of [18F]fluoride (t1/2: 110 min). In most cases, indirect radiolabeling is used for these more sensitive biomacromolecules due to the harsh conditions (i.e., organic solvents, high

From supramolecular chemistry to the nucleosome: studies in biomolecular recognition

• Marcey L. Waters

Beilstein J. Org. Chem. 2016, 12, 1863–1869, doi:10.3762/bjoc.12.175

• -translational modifications such as trimethyllysine are antibodies, but antibodies have significant limitations in this context, as they are too sequence specific. Thus, we aimed to develop synthetic receptors that would mimic the binding pockets of proteins to recognize trimethyllysine, but not the surrounding

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

Art, auto-mechanics, and supramolecular chemistry. A merging of hobbies and career

• Eric V. Anslyn

Beilstein J. Org. Chem. 2016, 12, 362–376, doi:10.3762/bjoc.12.40

• selectivity has been a goal for many studies using synthetic receptors, in part because Clark Still once noted that synthetic receptors could be as selective as antibodies [74], a chance lunch led me to consider moving in an entirely different direction toward the end of the 20th century. My ex-colleague, Dr

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

• options with antibodies and VEGF receptor inhibitors showed several clinical limitations, making the search for further clinically relevant targets and other drugs necessary to combat tumor-related angiogenesis. Secondary natural metabolites have also been identified as attractive candidates for the

• with anti-angiogenic activity have been intensively investigated. In addition to antibodies, several low molecular weight compounds have also been chemically and pharmacologically characterized and among them, several secondary metabolites of natural origin. In anti-angiogenic strategies, natural

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

• selective IgG antibodies that are cross-reactive with native MUC1 epitopes on MCF-7 human cancer cells. Keywords: cancer immunotherapy; fluorinated carbohydrates; glycoconjugates; MUC1; TACA; Introduction Since cancer has advanced to one of the leading causes of death in economical developed countries

• host [28]. Earlier studies proved that non-natural TACAs can be indeed highly immunogenic [29][30][31][32], although the elicited antibodies often failed to cross-react with the natural glycan. To overcome this drawback, the use of synthetic carbohydrate-based vaccines with TACA analogs [33][34] in

• glycoengineering, the structural integrity of the saccharide epitope must be maintained and cross-reactivity of the elicited antibodies with the native tumor-associated glycans is required. In this respect, the use of fluorinated TACAs [28][39][40][41][42] is a promising strategy due to the ability of C–F moieties

Preparation and evaluation of cyclodextrin polypseudorotaxane with PEGylated liposome as a sustained release drug carrier

• Kayoko Hayashida,
• Taishi Higashi,
• Daichi Kono,
• Keiichi Motoyama,
• Koki Wada and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2014, 10, 2756–2764, doi:10.3762/bjoc.10.292

• various targeting-ligands such as antibodies, sugars and folic acid to LPs [30][31][32]. Recently, stimulus responsive LPs such as bubble LPs, pH responsive LPs and thermoresponsive LPs have been developed as smart drug carriers [33][34][35]. PEGylated LP (PEG-LP) is one of the most popular LP products

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

• be efficiently utilized for the conjugation of short synthetic antigens bearing an amino spacer [26][27]. The synthesized CRM197 glycoconjugates were first tested for their capability of eliciting anti MenX CPS antibodies in mice. The functional activity of the generated antibodies was then assessed

• moieties were incorporated in our positive control 17 and in the MenX CPS glycoconjugates recently reported to induce protective antibodies, respectively [18]. Thus, we deemed the loading of glycoconjugates 14–16 sufficient to determine in vivo their capability of eliciting anti-MenX CPS antibodies

• statistical difference (p 0.05) at the doses of 0.3 and 1 μg, respectively. The MenXDP15 conjugate 17 also induced anti-MenX CPS antibodies that were comparable each other at the two different doses (p 0.05). However, the IgG levels induced by the trimer conjugate 16 at both 0.3 and 1 μg dose were

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

• -SREAKKQVEKAL-KQLEDKVQ) consists of a short C-terminal peptide from the M protein (in bold), placed within a sequence derived from the GCN4 leucine zipper DNA binding protein of yeast, which is known to promote an α-helical structure [33]. This chimeric peptide has been shown to elicit systemic IgG antibodies