Drug targeting to decrease cardiotoxicity – determination of the cytotoxic effect of GnRH-based conjugates containing doxorubicin, daunorubicin and methotrexate on human cardiomyocytes and endothelial cells

• Livia Polgár,
• Eszter Lajkó,
• Pál Soós,
• Orsolya Láng,
• Marilena Manea,
• Béla Merkely,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 1583–1594, doi:10.3762/bjoc.14.136

• peptide and of the type of the linkage on the toxic effect. Dau was coupled to the GnRH-III derivatives via oxime linkage in all cases. The oxime ligation was carried out under slightly acidic (pH 5) conditions [26] and the drug was attached directly either to GnRH-III (4) or to its derivatives in which

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

• a non-binding mutant of the target CTB protein [66], oxidised the N-terminal threonine residue of each subunit to an aldehyde and then chemically attached GM1os ligands by oxime ligation (Figure 15). This neoglycoprotein was able to display the five copies of the carbohydrate ligand with appropriate

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

• (CuAAC) and oxime ligation. This method was applied to the conjugation of biotin and β-linked galactose residues to yield an enzymatically active thermophilic lipase, which revealed specific binding to Erythrina cristagalli lectin by SPR binding studies. Keywords: chemoselectivity; dual protein

• conjugated with biotin using oxime ligation, by which the protein scaffold was immobilized on a streptavidin gold chip to monitor carbohydrate–protein binding studies by surface plasmon resonance (SPR). This immobilization strategy allowed easy handling and reproducible orientation, which are notable

• amino acids like glycine, alanine or serine in the native process of N-terminal methionine excision (NME) [43]. This process exposes Ser2 at the N-terminus for subsequent N-terminal oxime ligation. It has to be noted that the incorporation of Aha, as known [42][44], can hamper NME and therefore delivers

Bifunctional dendrons for multiple carbohydrate presentation via carbonyl chemistry

• Davide Bini,
• Francesco Nicotra and
• Laura Cipolla

Beilstein J. Org. Chem. 2014, 10, 1686–1691, doi:10.3762/bjoc.10.177

• of the glycoconjugation to the G0 dendron and G1 dendron by reductive amination, we decided to evaluate the possibility to obtain better conjugation yields by oxime ligation. Thus, G0, G1 and G2 dendrons 1–3 were reacted with α-O-L-fucopyranosyloxyamine (5) in citrate buffer at pH 3.5 [20] (Scheme 4

• quantitative yields. Conclusion In conclusion, novel G0, G1 and G2 dendrons suitable for glycoconjugation by carbonyl chemistry were synthesized. The conjugation of the saccharide by reductive amination was characterized by a low efficiency. On the other hand, the oxime ligation afforded the glycoconjugated

• : a) 4, 3 M Na2SO4, AcOH, NaCNBH3, EtOH, 80 °C, 6 h. Dendron conjugation to fucose via oxime ligation (buffer = citrate buffer). Supporting Information Supporting Information File 546: Experimental part. Acknowledgements This research was financially supported by the Cariplo Fundation under the

Multivalent display of the antimicrobial peptides BP100 and BP143

• Imma Güell,
• Rafael Ferre,
• Kasper K. Sørensen,
• Esther Badosa,
• Iteng Ng-Choi,
• Emilio Montesinos,
• Eduard Bardají,
• Lidia Feliu,
• Knud J. Jensen and
• Marta Planas

Beilstein J. Org. Chem. 2012, 8, 2106–2117, doi:10.3762/bjoc.8.237

• active against human red blood cells pointing out that peptide preassembly is critical for the hemolytic activity. Notably, peptide preassembly resulted in an enhanced bactericidal effect. Keywords: antimicrobial activity; carbopeptides; multimeric structures; oxime ligation; phytopathogenic bacteria

• CH3CN and acetate buffer (0.1 M, pH 4.76) at room temperature for 2 h, but the expected carbopeptide 3 was not obtained. Since the use of aniline as nucleophilic catalyst for oxime ligation has been described to enhance reaction rates by up to three orders of magnitude [31][32][33], we assayed the

• formation of 3 using the previous CH3CN/acetate buffer solution but containing aniline (100 mM). Under these conditions we could not detect the carbopeptide 3 even when increasing the reaction time up to 48 h. Results were improved by lyophilizing the template prior to the oxime ligation. In this case, the

Synthesis of heteroglycoclusters by using orthogonal chemoselective ligations

• Baptiste Thomas,
• Michele Fiore,
• Isabelle Bossu,
• Pascal Dumy and
• Olivier Renaudet

Beilstein J. Org. Chem. 2012, 8, 421–427, doi:10.3762/bjoc.8.47

• combinations of carbohydrates. By using both oxime ligation and copper(I)-catalyzed alkyne–azide cycloaddition, two series of compounds bearing binary combinations of αMan, αFuc or βLac in an overall tetravalent presentation, and either 2:2 or 3:1 relative proportions, have been prepared. Keywords

• methods, we decided to explore two chemoselective strategies to achieve this purpose. We first selected the oxime ligation since we have previously used this approach successfully for the preparation of sophisticated molecular systems, such as synthetic vaccines [27][28], immunomodulators [29], lectin

• , two copies of aminooxy αMan 1a, αFuc 2a and βLac 3a were coupled to 4, affording divalent oxime-linked compounds 5-Man, 5-Fuc, and 5-Lac, respectively. The oxime ligation was performed at 37 °C in aqueous acidic buffer with 2 equiv of sugars per anchoring site. After 3 h, complete reactions were