Design, automated synthesis and immunological evaluation of NOD2-ligand–antigen conjugates

• Marian M. J. H. P. Willems,
• Gijs G. Zom,
• Nico Meeuwenoord,
• Ferry A. Ossendorp,
• Herman S. Overkleeft,
• Gijsbert A. van der Marel,
• Jeroen D. C. Codée and
• Dmitri V. Filippov

Beilstein J. Org. Chem. 2014, 10, 1445–1453, doi:10.3762/bjoc.10.148

• incorporated SIINFEKL epitope on MHC-I molecules. However, stimulation of the NOD2 receptor in DCs was not sufficient to provide a strong immunostimulatory signal. Keywords: automated synthesis; glycopeptide; innate immunity; muramyl dipeptide; NOD2 receptor; solid phase synthesis; Introduction In recent

• (PRR-L) covalently bound to antigenic proteins and oligopeptides in the development of new (semi)synthetic vaccine modalities [3][4][5][6][7][8][9]. For instance, the group of Boons investigated a three-component conjugate containing a tumor-associated glycopeptide and a T cell epitope covalently bound

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

• glycoscience, because triazole-linked glycoconjugates can exhibit very interesting biological properties, offering a convenient access toward oligosaccharides, glycopeptide mimics, or multivalent carbohydrate systems [40][41][42][43][44][45][46][47][48]. Their further application in molcecular biosystems is

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

• oligomers varying the sugar (glucose, galactose, xylose) and sugar protecting groups. The influence of sugar units and the configuration of sugar-β-amino acids on β-peptide secondary structure were investigated by CD spectroscopy. Keywords: carbohydrate recognition; conformation; glycopeptide; β-peptide

• 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

• carbohydrate derived α,β-unsaturated ester [47][48][49][50]. In the present article, a new class of C-linked β-glycopeptide scaffolds 1–8 (Figure 2) were synthesized and investigated with respect to secondary structures, along with the influence of glycan modifications on peptide conformation [24][25], and the

A practical synthesis of long-chain iso-fatty acids (iso-C₁₂–C₁₉) and related natural products

• Mark B. Richardson and
• Spencer J. Williams

Beilstein J. Org. Chem. 2013, 9, 1807–1812, doi:10.3762/bjoc.9.210

• amides in natural products including septacidin [3], teicoplanins [4], tunicaminyluracil-based antibiotics [5] (tunicamycins [6], corynetoxins [7], and streptovirudins [8]), the arylomycin glycopeptide antibiotics [9][10], maradolipids [11], plipastatin-type lipopeptides [12], Nod factors [13

A new synthetic access to 2-N-(glycosyl)thiosemicarbazides from 3-N-(glycosyl)oxadiazolinethiones and the regioselectivity of the glycosylation of their oxadiazolinethione precursors

• El Sayed H. El Ashry,
• El Sayed H. El Tamany,
• Mohy El Din Abdel Fattah,
• Mohamed R. E. Aly,
• Ahmed T. A. Boraei and
• Axel Duerkop

Beilstein J. Org. Chem. 2013, 9, 135–146, doi:10.3762/bjoc.9.16

• ]. Glycosylamines are used also as enzyme inhibitors and vaccine precursors [18][19][20][21], and in glycopeptide synthesis [22][23] and in glycodendrimers and glycoclusters [24][25]. There are four structural isomers of glycosyl-thiosemicarbazides according to the location of the glycosyl residue on the

Antifreeze glycopeptide diastereomers

• Lilly Nagel,
• Carsten Budke,
• Axel Dreyer,
• Thomas Koop and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 1657–1667, doi:10.3762/bjoc.8.190

• , resistance to proteolytic degradation. Two AFGP mimetics were designed, one comprising exclusively D-configured amino acids and one containing allo-L-Thr. For the glycopeptide synthesis the amino acids Fmoc-D-Thr-OH and Fmoc-allo-L-Thr-OH were glycosylated with N-acetyl galactosamine and incorporated into

• 5, the retro-inverso AFGP analogue 7, and their corresponding aglycons 6 and 8 (Scheme 2) were analyzed be CD spectroscopy in water at room temperature and additionally at temperatures between −10 and +80 °C. The allo-L-threonine containing glycopeptide 5 shows a CD signature typical of a PPII-like

• )-configuration of the glycosylated allo-L-threonine obviously leads to changes of the conformation compared to glycopeptide 9 containing (2S,3R)-threonine. The temperature-dependent CD experiments of peptide 5 show an isodichroic point at λ ≈ 207 nm indicating a conformational transition (Figure 2a), presumably

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

• antibiotics [1][2], and of particular concern is the resistance to the cationic glycopeptide, vancomycin [3][4]. This challenge is being addressed in a number of ways, which include both detailed studies aimed at the further understanding of the mechanism of this resistance, as well as the development of new

• large glycopeptide analogues containing amine sites that can be protonated, such as telavancin, oritavancin and dalbavancin [5]. An alternative approach to meeting this resistance challenge, at least in part, is through the design and synthesis of smaller cationic peptidic compounds incorporating

Screening of ligands for the Ullmann synthesis of electron-rich diaryl ethers

• Nicola Otto and
• Till Opatz

Beilstein J. Org. Chem. 2012, 8, 1105–1111, doi:10.3762/bjoc.8.122

• , antifungal and herbicidal activity, rendering this compound class attractive for pharmaceutical and agrochemical research [1][2]. Prominent examples of bioactive natural representatives include the glycopeptide antibiotic vancomycin [3][4], the bisbenzylisoquinolines tubocurarine [5] and

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

• backbones, or mimics thereof, offer further possibilities to study protein-binding events. Keywords: glycopeptide binding; glycopeptides; glycoprotein synthesis; solid-phase peptide synthesis; synthetic vaccines; Introduction The majority of human proteins are co- or post-translationally modified by mono

• excellent reviews [6][7][8][9][10][11][12][13][14][15][16][17][18]. Review Glycopeptide-based vaccines Specific immune recognition, in which the glycan and the peptide backbone contribute to the binding epitope, is of particular interest for the development of safe immunotherapy and immunodiagnostics. Since

A bivalent glycopeptide to target two putative carbohydrate binding sites on FimH

• Thisbe K. Lindhorst,
• Kathrin Bruegge,
• Andreas Fuchs and
• Oliver Sperling

Beilstein J. Org. Chem. 2010, 6, 801–809, doi:10.3762/bjoc.6.90

• 1 fimbriae with a monovalent carbohydrate recognition domain (CRD) that is known from X-ray studies. However, binding studies with multivalent ligands have suggested an additional carbohydrate-binding site on this protein. In order to prove this hypothesis, a bivalent glycopeptide ligand with the

• capacity to bridge two putative carbohydrate binding sites on FimH was designed and synthesized. Anti-adhesion assays with the new bivalent ligand and type 1-fimbriated bacteria have revealed, that verification of the number of carbohydrate binding sites on FimH with a tailor-made bivalent glycopeptide

• strategy [25] was applied to connect the monosaccharide and the trisaccharide part of the bivalent glycopeptide target structure 1 (Figure 2). Accordingly, retrosynthetic analysis of 1 leads to the 2-azidoethyl glycosides 2 and 5, with the azido group masking an amino function; two pentaglycine spacer

Synthesis of glycosylated β³-homo-threonine conjugates for mucin-like glycopeptide antigen analogues

• Florian Karch and
• Anja Hoffmann-Röder

Beilstein J. Org. Chem. 2010, 6, No. 47, doi:10.3762/bjoc.6.47

• carbohydrate antigens (TACA) have proven to be important target structures for the development of molecularly defined anti-cancer vaccines. The strategic incorporation of β-amino acid building blocks into such mucin-type sequences offers the potential to create pseudo-glycopeptide antigens with improved

• amino acid tandem repeat sequence of MUC1 using sequential solid-phase glycopeptide synthesis, a first example of a mixed α/β-hybrid glycopeptide building block was obtained. The latter is of interest for the development of novel glycoconjugate mimics and model structures for anti-cancer vaccines with

• increased biological half-life. Keywords: glycopeptide; glycosylamino acids; β3-homo-threonine; MUC1 antigens; solid-phase synthesis; Introduction Glycosylation is the predominant co- and post-translational modification in higher organisms responsible for tailoring and fine-tuning of the activity of