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

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

• and glycopeptides are the key constituents of the cellular membrane and extracellular matrix, and play a pivotal role in various key cellular events such as cell–cell recognition, host–pathogen or host–symbiont interactions, molecular recognition of antibodies and metastasis [1][2][3][4][5]. The

Human dendritic cell activation induced by a permannosylated dendron containing an antigenic GM₃-lactone mimetic

• Renato Ribeiro-Viana,
• Elena Bonechi,
• Javier Rojo,
• Clara Ballerini,
• Giuseppina Comito,
• Barbara Richichi and
• Cristina Nativi

Beilstein J. Org. Chem. 2014, 10, 1317–1324, doi:10.3762/bjoc.10.133

• (Figure 1) was able to elicit in vivo antimelanoma antibodies [32]. More recently [33], we established that the multivalent presentation of this synthetic mimetic positively interferes with human melanoma cell (A375) adhesion, migration and resistance to apoptosis, showing a clear amplification of the

• incubation with LPS (1 µg/mL, Sigma–Aldrich), compound 5 and scaffold 7 (two doses, 50 and 10 µg/mL). DC phenotype The DC phenotype was analyzed by flow cytometry with a 4 color EpicsXL cytometer (Beckman–Coulter), equipped with Expo 32 software. Cell surface markers were labelled with monoclonal antibodies

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

• water cloud owing to the capability of every ethylene oxide unit to bind about three water molecules [110][111]. This leads to an improved solubility and to a remarkable shielding of the peptide against proteases and antibodies [112][113] that is reflected in an improved stability and biodistribution as

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• , they are interesting starting points for the development of novel drugs [1][2]. Peptides may act as neurotransmitters, hormones or antibodies and are involved in the progress of several diseases. However, natural peptides and proteins possess several properties which make them less suitable as a drug

SF002-96-1, a new drimane sesquiterpene lactone from an Aspergillus species, inhibits survivin expression

• Silke Felix,
• Louis P. Sandjo,
• Till Opatz and
• Gerhard Erkel

Beilstein J. Org. Chem. 2013, 9, 2866–2876, doi:10.3762/bjoc.9.323

• Diagnostics, Mannheim, Germany)). 25 µg total cell extracts were subjected to 10% SDS-PAGE, transferred onto a nitrocellulose membrane, probed with antibodies specific for human survivin (1:1000, 71G4B7, New England Biolabs Frankfurt/M) or β-actin (1:1000, 13E5, New England Biolabs Frankfurt/M) and then with

• IL-6 (for Stat3) and 10 ng/mL TNF-α, 5 ng/mL IL-1β (for NF-κB) for 30 min. Chromatin was cross-linked and immunoprecipitated using antibodies against Stat3, NF-κB p65, acetylated histone 3 (H3K9Ac) or rabbit IgG. DNA isolated from immunoprecipitates or from total chromatin preparation before

The regulation and biosynthesis of antimycins

• Ryan F. Seipke and
• Matthew I. Hutchings

Beilstein J. Org. Chem. 2013, 9, 2556–2563, doi:10.3762/bjoc.9.290

• monoclonal anti-His antibodies were unsuccessful because His6-σAntA does not complement the antA mutant strain of S. albus S4, suggesting the protein is inactive. Furthermore, polyclonal antibodies raised against purified σAntA reacted with the purified σAntA protein in immunoblotting experiments, but could

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

• cell homogenates, these compounds may be further used to investigate Hsp90 complexes in live cells, which represents a more physiologically relevant state. These tools also have use in flow cytometry and microscopy, whereby fluorescently labeled antibodies to biotin are used, as we describe below

Chemical modification allows phallotoxins and amatoxins to be used as tools in cell biology

• Jan Anderl,
• Hartmut Echner and
• Heinz Faulstich

Beilstein J. Org. Chem. 2012, 8, 2072–2084, doi:10.3762/bjoc.8.233

• oleic acid or polylysine and thus decrease the medium concentration necessary to achieve growth inhibition down to the nanomolar range. Amanitin as a drug bound to tumor monoclonal antibodies, has recently been described for the therapy of adenocarcinomas [34]. Coupling to methoxypolyethyleneglycol has

Peptides presenting the binding site of human CD4 for the HIV-1 envelope glycoprotein gp120

• Julia Meier,
• Kristin Kassler,
• Heinrich Sticht and
• Jutta Eichler

Beilstein J. Org. Chem. 2012, 8, 1858–1866, doi:10.3762/bjoc.8.214

• range of broadly neutralizing anti-HIV-1 antibodies, such as mAb b12 [7] and mAb VRC01 [8], overlap the CD4 binding site (CD4bs) of gp120, making this region of gp120 an important target for immunogen design. Therefore, we have previously designed and generated a synthetic peptide that presents the

• involving recombinant proteins, i.e., gp120, and soluble CD4 (sCD4) presenting the extracellular CD4 domains, in conjunction with the use of antibodies that recognize the coreceptor binding site of gp120 (CD4i antibodies) as coreceptor surrogates [8]. Similar to sCD4, the cyclic peptide CD4-M5, which

Synthesis of 4” manipulated Lewis X trisaccharide analogues

• Christopher J. Moore and
• France-Isabelle Auzanneau

Beilstein J. Org. Chem. 2012, 8, 1134–1143, doi:10.3762/bjoc.8.126

• -GlcNAcp), at the nonreducing end, and this antigenic determinant is also present at the surface of many normal cells and tissues, which include kidney tubules, gastrointestinal epithelial cells, and cells of the spleen and brain [7][8][9][10][11]. Indeed, anti-Lex monoclonal antibodies (e.g., FH3, SH1

• consider is an expected autoimmune response to the native Lex antigen. Fortunately an internal epitope displayed by dimLex was discovered when monoclonal antibodies (mAbs) FH4 and SH2, raised against dimLex, were isolated. Indeed, these mAbs were shown to bind to the dimLex and trimLex antigens but only

• weakly recognise Lex trisaccharide antigen [1][2][3][4][5][6]. With this in mind, we focus our research on the discovery of analogues of dimLex that can be used as safe vaccine candidates. Ideally, these analogues should display the internal epitopes that are recognized by anti-dimLex SH2-like antibodies

The use of glycoinformatics in glycochemistry

• Thomas Lütteke

Beilstein J. Org. Chem. 2012, 8, 915–929, doi:10.3762/bjoc.8.104

• , classifications, and information regarding related diseases. GlycoEpitopeDB provides information on antibodies that recognize specific carbohydrate epitopes and glycoproteins or glycolipids that are known to carry the epitopes. A frequently used technique to study the epitopes, to which a GBP binds, are glycan

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

• applications, in which glycopeptides or glycoproteins serve as tools for biological studies, are reviewed. The importance of specific antibodies directed to the glycan part, as well as the peptide backbone has been realized during the development of synthetic glycopeptide-based anti-tumor vaccines. The fine

• a number of cases [28][29][34]. Furthermore, several antibodies induced by the vaccines showed specific recognition of tumor cells. The MUC1 tandem repeat glycopeptides were synthesized on solid-phase, according to the Fmoc strategy, by using Fmoc protected amino acids and Fmoc glycosyl amino acid

• T-antigen, or a difluoro-T-antigen on different positions in the tandem repeat (6–10), showed that high antibody titers were induced in almost all of the immunized mice. Evaluation of the generated antibodies provided evidence that specific immune responses were elicited towards the MUC1 antigens

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

• Grazia Marano,
• Claas Gronewold,
• Martin Frank,
• Anette Merling,
• Christian Kliem,
• Sandra Sauer,
• Manfred Wiessler,
• Eva Frei and
• Reinhard Schwartz-Albiez

Beilstein J. Org. Chem. 2012, 8, 787–803, doi:10.3762/bjoc.8.89

• oligosaccharides interacting with the respective binding partners on neighboring cells. In this respect our results are reminiscent of a previous study in which we described the inhibition of endothelial networking by monoclonal antibodies against the histo blood group oligosaccarides Lewisy and H and further by

Triterpenoid saponins from the roots of Acanthophyllum gypsophiloides Regel

• Elena A. Khatuntseva,
• Vladimir M. Men’shov,
• Alexander S. Shashkov,
• Yury E. Tsvetkov,
• Rodion N. Stepanenko,
• Raymonda Ya. Vlasenko,
• Elvira E. Shults,
• Genrikh A. Tolstikov,
• Tatjana G. Tolstikova,
• Dimitri S. Baev,
• Vasiliy A. Kaledin,
• Nelli A. Popova,
• Valeriy P. Nikolin,
• Pavel P. Laktionov,
• Anna V. Cherepanova,
• Tatiana V. Kulakovskaya,
• Ekaterina V. Kulakovskaya and
• Nikolay E. Nifantiev

Beilstein J. Org. Chem. 2012, 8, 763–775, doi:10.3762/bjoc.8.87

• bark, or without an adjuvant, and the specific anti-3’SL IgM and IgG responses were evaluated. For saponins 1 and 2, a significant specific response was observed in comparison with the control vaccine formulation with antigen alone (Table 6). High serum titers of IgM and IgG antibodies were registered

• in the vaccination with compound 1 as adjuvant, though the IgG level did not achieve the level measured in the experiment with saponin from Quillaja bark. Titers of those antibodies in the experiment with saponin 2 were rather low. We can conclude, that in combination with 3’SL-KLH, antigen compound

Chemo-enzymatic modification of poly-N-acetyllactosamine (LacNAc) oligomers and N,N-diacetyllactosamine (LacDiNAc) based on galactose oxidase treatment

• Christiane E. Kupper,
• Ruben R. Rosencrantz,
• Birgit Henßen,
• Helena Pelantová,
• Stephan Thönes,
• Anna Drozdová,
• Vladimir Křen and
• Lothar Elling

Beilstein J. Org. Chem. 2012, 8, 712–725, doi:10.3762/bjoc.8.80

• summary, these novel neo-glycoconjugates are interesting tools for extensive binding studies of a variety of glycan binding proteins (lectins, antibodies) and for possible therapeutic applications. Conclusion Novel poly-LacNAc derivatives have been produced on a micro-gram scale, which can be used for

Convergent synthesis of the tetrasaccharide repeating unit of the O-antigen of Shigella boydii type 9

• Abhishek Santra and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2011, 7, 1182–1188, doi:10.3762/bjoc.7.137

• therapeutics than the earlier used anti-shigellosis agents [9][10]. Because of the high antigenic nature of the O-antigens, antibodies against the O-specific polysaccharide of a particular Shigella strain have the potential to control Shigella infections [11][12][13][14]. A number of reports have been cited

Catalysis: transition-state molecular recognition?

• Ian H. Williams

Beilstein J. Org. Chem. 2010, 6, 1026–1034, doi:10.3762/bjoc.6.117

• objectives, such as the design of TS analogues as potential drugs, or the design of synthetic catalysts (including catalytic antibodies), require prior knowledge of the TS structure to be mimicked. Examples, both old and new, of computational modelling studies are discussed, which illustrate this fundamental

• decrease in the energy of activation” [4]. A corollary to this insight was provided by W. P. (Bill) Jencks, who noted that a catalyst might be synthesised by raising an antibody to a hapten resembling the TS of the reaction to be catalysed: “the combining sites of such antibodies should be complementary to

• expected to compete successfully with the substrate in combining with the enzyme, which in this respect would be similar in behaviour to antibodies; but an enzyme complementary to a strained substrate molecule would attract more strongly to itself a molecule resembling the strained substrate molecule than

Synthesis of 6-PEtN-α-D-GalpNAc-(1–>6)-β-D-Galp-(1–>4)-β-D-GlcpNAc-(1–>3)-β-D-Galp-(1–>4)-β-D-Glcp, a Haemophilus influenzae lipopolysacharide structure, and biotin and protein conjugates thereof

• Andreas Sundgren,
• Martina Lahmann and
• Stefan Oscarson

Beilstein J. Org. Chem. 2010, 6, 704–708, doi:10.3762/bjoc.6.80

• , i.e. the bacteria express common human carbohydrate structures on their surface that the host recognises as self-structures and do not produce antibodies against. Construction of a glycoconjugate vaccine against NTHi is thus quite complex. Carbohydrate structures that are both exposed on the surface

• examined. Compound 23 was also biotinylated for use in ELISA-screening of antibodies raised against native LPS. Reaction with the commercial NHS-activated ester of biotin followed by TFA-treatment to remove the Boc-group afforded derivative 25. The H. influenzae outer core target structure. i. BH3, Bu2BOTf

RAFT polymers for protein recognition

• Alan F. Tominey,
• Julia Liese,
• Sun Wei,
• Klaus Kowski,
• Thomas Schrader and
• Arno Kraft

Beilstein J. Org. Chem. 2010, 6, No. 66, doi:10.3762/bjoc.6.66

• where antibodies are generated in response to minute amounts of foreign antigens. A continual challenge in nanoscale chemistry is to mimic the biological molecular recognition functions by synthetic chemistry with the aim of producing systems of lower complexity. When successful, this will enable the

An expedient synthesis of 5-n-alkylresorcinols and novel 5-n-alkylresorcinol haptens

• Kirsti Parikka and
• Kristiina Wähälä

Beilstein J. Org. Chem. 2009, 5, No. 22, doi:10.3762/bjoc.5.22

• describes the synthesis of two 1-phenylalkenes in 20–30% yield using benzaldehyde and a CH2Cl2/H2O solvent [31]. We report here a fast and efficient synthesis of the long chain 5-n-alkylresorcinols 1 and the new potential hapten derivatives of 5-n-alkylresorcinols 2, ready for the development of antibodies

Synthesis of imidazol- 1-yl-acetic acid hydrochloride: A key intermediate for zoledronic acid

• Santosh Kumar Singh,
• Narendra Manne,
• Purna Chandra Ray and
• Manojit Pal

Beilstein J. Org. Chem. 2008, 4, No. 42, doi:10.3762/bjoc.4.42

• . Zoledronic acid is also used along with the cancer chemotherapy to treat bone damage caused by multiple myeloma (a type of cancer of plasma cells that are part of the immune system cells in bone marrow and produce antibodies) or by cancer that began in another part of the body but has spread to the bones

Colchitaxel, a coupled compound made from microtubule inhibitors colchicine and paclitaxel

• Karunananda Bombuwala,
• Thomas Kinstle,
• Vladimir Popik,
• Sonal O. Uppal,
• James B. Olesen,
• Jose Viña and
• Carol A. Heckman

Beilstein J. Org. Chem. 2006, 2, No. 13, doi:10.1186/1860-5397-2-13

• Laboratories (San Francisco, CA), was diluted 1:100. As secondary antibodies, FITC-conjugated (U. S. Biochemical Corp., Cleveland, OH) or Alexa 488-conjugated goat anti-mouse immunoglobulin G (Molecular Probes, Eugene, OR) were used as described previously [17]. Wide-field fluorescence images were recorded on