On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• utilization of paclitaxel are its high hydrophobicity, requiring suitable vehicles to effectively deliver it to tumor tissues, and the development of multidrug resistance due to the P-glycoprotein-mediated efflux [85][92]. Paclitaxel stabilizes microtubules by binding specifically to the beta-tubulin subunit

Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

• Sabine Schuster,
• Beáta Biri-Kovács,
• Bálint Szeder,
• Viktor Farkas,
• László Buday,
• Zsuzsanna Szabó,
• Gábor Halmos and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64

• regulatory pituitary glycoprotein luteinizing hormone (LH) and follicle stimulating hormone (FSH) which act on the gonads and regulate the production of the sex steroids androgen and estrogen [2]. In the last decades a large number of synthetic GnRH-I-analogues has been designed with the purpose to interact

Carbohydrate inhibitors of cholera toxin

• Vajinder Kumar and
• W. Bruce Turnbull

Beilstein J. Org. Chem. 2018, 14, 484–498, doi:10.3762/bjoc.14.34

• spacing’s to maximize interactions with the target protein. Dynamic light scattering and analytical ultracentrifugation demonstrated that the glycoprotein formed a 1:1 complex with the target CTB protein and was highly effective as an inhibitor with an IC50 value of 104 pM. Multivalent inhibitors with more

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• interconversions, and peracetylation were followed by conversion to the oxazoline, using TMSBr, BF3·Et2O and collidine, and finally deacetylation. It was found that the incorporated azide was tolerated by the ENGase enzyme (Endo A), and so a modified glycoprotein (RNase) was made by enzymatic attachment of this

• respect to total synthesis. Neither Kajihara nor others have yet to employ these routes to the production of N-glycan oxazolines. The soy bean approach Soy bean agglutinin is a glycoprotein decorated with high mannose glycans [96]. Isolation of soy bean agglutinin from unroasted soy bean flour is achieved

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• constituted the key step of a nine-step total synthesis of the eastern fragment of jatrophane diterpene Pl-3, which is a complex natural product with high promising biological activities, such as antiproliferative activity and inhibition of the efflux-pump activity of multidrug resistance P-glycoprotein. The

What contributes to an effective mannose recognition domain?

• Christoph P. Sager,
• Deniz Eriş,
• Martin Smieško,
• Rachel Hevey and
• Beat Ernst

Beilstein J. Org. Chem. 2017, 13, 2584–2595, doi:10.3762/bjoc.13.255

• is the highly mannosylated glycoprotein uroplakin 1a (UPIa) [35][36]. The binding pocket of FimH accommodates a single α-D-mannose (1) with an extended hydrogen-bond network [37][38]. Accordingly, any modifications on the hydroxy groups of the mannose virtually abolish binding affinity [37][38][39

• of oligomannosides on viral envelop glycoprotein gp120, facilitating stronger adhesion between dendritic cells and HIV-1 [43][75][76]. This multivalent binding interaction results in an enhancement in binding by several orders of magnitude, from a KD of 26 μM for monovalent Man9GlcNAc2, as compared

• carbohydrate-based drugs. One such example of a therapeutic application can be found in a recent novel approach to treating anti-myelin-associated glycoprotein (anti-MAG) neuropathy, a rare, disabling autoimmune disorder. The use of a multivalent glycopolymer mimicking the natural HNK-1 epitope proved to be a

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• example of this powerful methodology has been reported from the Fairbanks group [16] recently. They synthesized a phosphorylated glycoprotein containing a mannose-6-phosphate (M6P)-terminated N-glycan (Scheme 3). Their work combined the chemical synthesis of a phosphotetrasaccharide with the enzymatic

• glycoproteins would be a tremendous advancement in the field. The major drawback, however, is that the authors did not isolate the purified glycoprotein; their yield is based solely on the ESIMS analysis of the crude reaction mixture. It is also known that Lawesson’s reagent is not compatible with a C2 NAc

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

• the surface of the protein. For a given glycoprotein, there may exist considerable variations of N-linked glycan chains from protein to protein. Such a heterogeneous macromolecular mix is not suitable for crystal formation. Large post-translational modifications also have the effect of increasing

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

• on the identification of sugar epitopes of the surface envelope glycoprotein of HIV-1, capable of eliciting a protective response. GAuNPs coated with high-mannose type oligosaccharide of HIV-1 gp120, were prepared as glycoconjugate systems able to mimic the natural presentation of gp-120 high-mannose

• of mucin glycoprotein on the surface of cancer cells, which are characterized by a dense presentation of glycans attached to a protein backbone. So, multicopy–multivalent polymeric versions of the tumor-associated α-GalNAc (Tn) antigen, obtained through RAFT polymerization, were prepared and used to

• family of glycosylated proteins with a high molecular weight, produced by epithelial tissues. The most studied is the membrane-bound glycoprotein MUC1, a glycoprotein with extensive O-linked glycosylation in its extracellular domain. The authors demonstrated that the multivalent presentation of MUC1

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

• but not the terminal trimming of N-glycans is involved in the regulation of the correct membrane glycoprotein folding since the inhibition of N-glycosylation processing by 1-deoxymannojirimycin (dMM) results in a mannose-rich type of N-glycan that does not affect either the protein stability or

Biomimetic synthesis and HPLC–ECD analysis of the isomers of dracocephins A and B

• Viktor Ilkei,
• András Spaits,
• Anita Prechl,
• Áron Szigetvári,
• Zoltán Béni,
• Miklós Dékány,
• Csaba Szántay Jr,
• Judit Müller,
• Árpád Könczöl,
• Ádám Szappanos,
• Attila Mándi,
• Sándor Antus,
• Ana Martins,
• Attila Hunyadi,
• György Tibor Balogh,
• György Kalaus (†),
• Hedvig Bölcskei,
• László Hazai and
• Tibor Kurtán

Beilstein J. Org. Chem. 2016, 12, 2523–2534, doi:10.3762/bjoc.12.247

• the other hand, the possibility for neuroprotective activity could not be tested with the applied experimental setup. As an additional bioassay on compounds 2a–d and 3a–d, their potential to interfere with the function of P-glycoprotein (P-gp) was tested. By transporting a wide variety of compounds

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

• (ΔG‡r) using the Eyring model. The found ΔG‡r values (17.9–18.3 kcal/mol) were in good accordance with those of other known PNA-derivates (17.9–19 kcal/mol). The PNA-based glycoprotein building blocks described here will be used in combination with previously described benzoic acid-based glycopeptoids

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• derivatives 12 and 13. Phenylnannolone A was proven to restore daunorubicin sensitivity in cancer cells by inhibiting P-glycoprotein (P-gp), an ATP-binding cassette transporter (ABC transporter). In tumor cells, P-gp serves as an efflux transporter of drugs, ultimately leading to treatment failure [46]. Apart

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

• pharmacologic activities were reported for them. Thus, cholesterol-conjugated C-peptides, for example IV, are potent inhibitors of the Ebola virus glycoprotein-mediated cell entry [16], while cholesterol-derived amines exhibited a strong antiviral activity against the influenza A virus (IFV). These amines were

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

• engineer multivalent glycoprotein conjugates, we have used the incorporation of non-canonical amino acids (NCAA) [13] by supplementation based incorporation (SPI) [14][15][16][17] in auxotroph expression systems followed by the chemoselective Cu-catalyzed azide–alkyne cycloaddition (CuAAC) to attach

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

• ) through bivalent binding of 90K/Mac-2BP, a cell surface glycoprotein [29]. To further the understanding of structural specificity in binding events, Iurisci et al. designed multivalent oligosaccharide ligands to inhibit galectin-1 induced homotypic cellular aggregation in the A375 cell line [30]. Belitsky

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

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

• scientific community. The tumor-associated glycoprotein MUC1 represents a well-established target for cancer immunotherapy and has been used for the construction of various synthetic vaccine candidates. However, many of these vaccine prototypes suffer from an inherent low immunogenicity and are susceptible

• cells from healthy ones by means of tumor-associated antigens (TACA), e.g., partial structures of the mucin glycoprotein MUC1 [6][7]. Cancer-associated MUC1 is characterized by the presence of specifically altered carbohydrate side chains in its extracellular tandem-repeat domain due to fundamental

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

• removal and the replenishment of cholesterol from cells treated by DHA. The methylated β-CD removes not only cholesterol but also some phospholipids from the membrane thus inhibiting the efflux function of P-glycoprotein [24][25], and at higher concentrations induces apoptosis in the rat alveolar cell

• for monitoring DC activation based on its glycoprotein nature and the potential to act as both an activation and supression marker of DC depending on its monomeric or dimeric forms [45]. These functional attributes of CD83 offered us a potential tool for dissecting the protein and lectin mediated

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• ]. Iminosugars have shown a variety of biological effects including inhibiting glycosidases and glycoprotein-processing enzymes. Onomura and Matsumura and colleagues have used the anodic methoxylation and mild acid treatment strategy to prepare the initial starting materials in the synthetic campaign (Scheme 17

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

• subsequently reconstituted with 10 mM NaPi pH 7. Yields (recovered glycoprotein as determined by microBCA, Pierce Thermo): 85–95%. Loading of glycoconjugate was determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI–TOF MS; UltraFlex III MALDI–TOF/TOF instrument

Multivalent scaffolds induce galectin-3 aggregation into nanoparticles

• Candace K. Goodman,
• Mark L. Wolfenden,
• Pratima Nangia-Makker,
• Anna K. Michel,
• Avraham Raz and
• Mary J. Cloninger

Beilstein J. Org. Chem. 2014, 10, 1570–1577, doi:10.3762/bjoc.10.162

• Warren Avenue, Detroit, Michigan 48201, USA 10.3762/bjoc.10.162 Abstract Galectin-3 meditates cell surface glycoprotein clustering, cross linking, and lattice formation. In cancer biology, galectin-3 has been reported to play a role in aggregation processes that lead to tumor embolization and survival

• indicated that the glycoprotein ligand could serve to initiate aggregation, but carbohydrate binding was not required for all of the galectin-3 lectins that were involved in the interaction. Some galectin-3/galectin-3 interactions, in addition to carbohydrate/galectin-3 interactions, were proposed [18]. A

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

• transferred to a glycan acceptor in a glycoprotein by a sialyltransferase [32][33]. A chemoenzymatic method for its preparation is shown in Scheme 1. It is based on the coupling of Fmoc-glycyl-mannosamine with pyruvate catalized by SA-aldolase to afford the N-protected sialic acid. After reaction with CTP

• catalyzed by CMP-sialic acid synthetase, the nucleotide is deprotected and the free amine is utilized as a locus to PEG attachment. The introduction of the PEGylated sialic acid into the glycoprotein takes place in two steps. First, an O-glycan is introduced enzymatically and second, PEGylated sialic acid

• PEGylation of a glycoprotein can be performed in three steps. First, the sialic acid is removed from the native protein with a sialidase and subsequently Sia-PEG is transfered to the uncovered terminal Gal units of the linked glycan taking advantage of the substrate promiscuity of the sialyltransferase

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

• aggregates in aqueous solution was about 1 μm (data not shown). The antiviral activity of biantennary glycopeptides was studied by means of a fetuin binding inhibition test (FBI-test) [17] (the glycoprotein fetuin contains several sialylated carbohydrate chains). In this test, the glycopeptides inhibited the

Molecular architecture with carbohydrate functionalized β-peptides adopting 3₁₄-helical conformation

• Nitin J. Pawar,
• Navdeep S. Sidhu,
• George M. Sheldrick,
• Dilip D. Dhavale and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2014, 10, 948–955, doi:10.3762/bjoc.10.93

• conformationally constrained and well-defined scaffold for sugar presentation on a 314-helix [18][19][20] as well as on a β-peptide 312-helical scaffold obtained by oligomerization of glycosylated pyrrolidine β-amino acids [35]. Glycopeptide or glycoprotein synthesis is challenged by different conditions required