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

• investigated in the mouse model using ovalbumin as an antigen. Their activities were compared to the previously described mannosylated adamantane-containing desmuramyl peptide and peptidoglycan monomer. Tested compounds exhibited adjuvant activity and the strongest enhancement of IgG production was stimulated

• innate immunity through macrophage response as well as to more distally affect adaptive immunity through the production of antigen-specific T cells [5]. MDP binding to NOD2 has been confirmed [6] as well as the crystal structure of NOD2 in the inactive ADP-bound state [7]. MDP is the structural fragment

• with derivatives lacking the adamantane moiety. Immunostimulating properties of synthesized derivatives were assessed in vivo using ovalbumin as an antigen. Results and Discussion Design Desmuramyl peptides enter into the cell by passive absorption and this process depends on lipophilicity [25

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

• admixture vaccine was able to blunt nociception incurred from either drug, however, we also realized the challenges of navigating through FDA approval of a combination vaccine. As such we pondered whether singular antigen presentation of both drugs in close proximity would still be able to entice a

• µL whole blood. All sera were tested against both Her-BSA and Fent-BSA antigens, and sera from each chemically contiguous vaccine group were tested against their own antigen. For heroin analysis, 6-acetylmorphine (6-AM) was used as the primary analyte in surface plasmon resonance (SPR) analysis as it

Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase

• Robert J. Kempton,
• Taylor A. Kidd-Kautz,
• Soizic Laurenceau and
• Stefan Paula

Beilstein J. Org. Chem. 2019, 15, 971–975, doi:10.3762/bjoc.15.94

• protease PSA (prostate-specific antigen) that is capable of cleaving the peptide bond between Gln and Leu, thereby producing an active TG analogue that can enter the cancer cell and kill it by triggering apoptosis. Apoptosis occurs as the result of elevated cytosolic calcium levels, which are caused by

Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

• Chelsea L. Rintelmann,
• Tara Grinnage-Pulley,
• Kathleen Ross,
• Daniel E. K. Kabotso,
• Angela Toepp,
• Anne Cowell,
• Christine Petersen,
• Balaji Narasimhan and
• Nicola Pohl

Beilstein J. Org. Chem. 2019, 15, 623–632, doi:10.3762/bjoc.15.58

• system recognizes parasite surface glycoconjugates, or pathogen-associated molecular patterns (PAMPs), to build an immune response against the parasite and impede disease progression. Antigen presenting cells (APCs) recognize these PAMPs as pathogenic as compared to host glycans making these moieties

• -labile probe was found to increase T cell production, suggesting α-1,2-trimannose antigen presentation at the major histocompatibility complex II (MHC II) [41]. Based on our previous studies [11][40][41][42], we sought to design and synthesize a new Leishmania-associated molecular probe that could allow

• intracellular monitoring and validation of T cell antigen presentation. This new probe would also be linked to the surface of a polyanhydride copolymer microparticle based on 1,6-bis(p-carboxyphenoxy)hexane (CPH) and sebacic anhydride (SA) to allow for enhanced internalization and uptake of the immunogenic

Synthesis of α-D-GalpN₃-(1-3)-D-GalpN₃: α- and 3-O-selectivity using 3,4-diol acceptors

• Emil Glibstrup and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2018, 14, 2805–2811, doi:10.3762/bjoc.14.258

• and present in several distinct entities. One of the most studied glycoconjugates, containing this sequence, is the Forssman antigen, in which this disaccharide is the terminal unit. The many biological roles attributed to this particular glycoconjugate and its appearance in some human tumors [1][2

• ] has triggered the interest of carbohydrate chemists since the early days of complex oligosaccharides synthesis. The structure of the pentasaccharide part of the Forssman antigen was resolved in the seventies [3][4] and soon thereafter Paulsen and Bünsch finished the chemical synthesis of the

• pentasaccharide chain [5][6]. The pioneering work by Paulsen was later followed up by a total synthesis by the Ogawa group [7] and an oligosaccharide synthesis by the Magnusson group [8]. With the increasing understanding of glycobiology, the Forssman antigen has remained an interesting target for vaccine

Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer

• Sagnik Sengupta,
• Mena Asha Krishnan,
• Premansh Dudhe,
• Ramesh B. Reddy,
• Bishnubasu Giri,
• Sudeshna Chattopadhyay and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244

• membrane antigen (PSMA) expressed on prostate, breast, bladder and brain cancers and pteroate rhodamine B, targeting folate receptor positive cancers such as ovarian, lung, endometrium as well as inflammatory diseases have been synthesized. In vitro studies using LNCaP (PSMA +ve), PC-3 (PSMA −ve, FR −ve

• membrane antigen (PSMA) [7][8][9] and the folate receptor [10][11][12][13] are well characterized and most attractive cancer biomarkers present in primary and metastatic stages of prostate and ovarian cancers, respectively. PSMA belongs to a family of type II membrane bound glycoprotein over-expressed on

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• towards oligosaccharides, which would also contribute to the identification and development of drug candidates. For example, cancer immunotherapy based on vaccines derived from carbohydrate antigen–adjuvant combinations has received much attention in recent years [75][76][77]. However, the difficulties

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

• , known as T antigen nouvelle (Tn antigen), is further modified by the β(1→3) attachment of galactose leading to the Thomsen–Friedenreich (TF) antigen [6][7]. These two immunodeterminants are overexpressed on a high number of different cancer cells, located in the breast, lung, colon, liver, prostate and

• gastric tissues [8]. Furthermore, the TF-antigen region serves as the core region for the ABO and Lewis blood group determinants [9]. The high importance of GalNAc in diverse biological processes, together with its notable role in drug development, turns this compound into an interesting synthetic target

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

• ), HIV and HVB (hepatitis B virus surface antigen) in a single tube was demonstrated [141]. Addition of a very low concentration of bovine serum albumin (BSA, 0.01%) was shown to enhance the performance of the PNA–GO-based DNA sensing platform by reducing the non-specific adsorption of PNA–DNA duplexes

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

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

• major surface antigen of Gram-negative bacteria, a complex heterogeneous glycolipid lipopolysaccharide (LPS, or endotoxin) [2][3], is recognised by a receptor complex composed of Toll-like Receptor 4 (TLR4) and a co-receptor protein myeloid differentiation factor 2 (MD-2) which are expressed by

• micro-heterogeneous structure distinguished by three regions: the lipid A [5], the core oligosaccharide [6] and the O-antigen [7] (Figure 1B). The TLR4·MD-2 receptor complex senses picomolar amounts of LPS and initiates the biosynthesis of diverse mediators of inflammation (such as tumor necrosis factor

• integrity and antigen presentation, decreases susceptibility to antimicrobial peptides and enhances pathogenicity [25]. In some LPS, the lipid A phosphates are post-translationally modified by substitution with the compounds that reduce the net negative charge of LPS, such as phosphoethanolamine in E. coli

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

• binding site pre-organization, are more difficult to assess and accordingly have been highlighted in this review. Mannose-binding CLECs are involved in various pathways of the human innate immune response, including the blood dendritic cell antigen 2 (BDCA-2, also known as CD303) [18], langerin (CD207

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• properties (Figure 3B) [49]. Some phosphonic acid-containing compounds were also used for their herbicidal properties as exemplified by glyphosate (11) [50] (Figure 3C). Finally, in the field of immunotherapy, γδ T cells, at the difference to αβ T cells, respond to non-peptidic antigen or to the alterations

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• oligosaccharides including those containing both 1,2-cis and 1,2-trans linkages, branching sequences and sulfate esters. For example, a four component preactivation-based one-pot synthesis was designed to synthesize Globo-H, an important tumor-associated carbohydrate antigen (Scheme 18) [60]. Globo-H

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

• that bind to internal carbohydrate motifs. This is a mechanism typically found in bacterial polysaccharides. There is an occurrence of very large cavities which are open at both ends. The “side-on” entry of the antigen is often at the origin of the occurrence of conformational antigens

From chemical metabolism to life: the origin of the genetic coding process

• Antoine Danchin

Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111

• antigen–antibody interactions during the immune response [40]. Complementarity illustrates a formal correspondence that may be used subsequently as a recognition signal. It manages information as signals in sensor–receptor interactions. This is exploited in living organisms in the way sensors monitor

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

• carriers, to target antigens to DCs via lectins, a well-known strategy explored in immunotherapy. GAuNPs in vaccine development AuNPs engineering is offering significant contribution to immunology also in vaccine development. The repetitive antigen display is the key point related to this nanotechnology

• 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

• protein component. In a different example, Barchi and co-workers focused on the Thomsen Friedenreich tumor-associated antigen (TFag) and synthesized TFag-amino acid-coated AuNPs by means of a thiol-polyethylene glycol spacer. Among the synthesized GAuNPs, TFag-Thr-AuNPs showed, in vitro, an increased

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

• ] strategy that was not successful due to steric constraints. The synthetic hexasaccharide is the starting point for further immunological investigations. Keywords: carbohydrate antigen; glycosylation; oligosaccharides; Streptococcus pneumoniae; total synthesis; Introduction Streptococcus pneumoniae is a

• immunological analysis of S. pneumoniae serotype 12F can be undertaken, and future work will address the expanded inclusion of this antigen in next-generation glycoconjugate vaccines. Abbreviations Ac: acetate ester; BAIB: bis(acetoxy)iodobenzene; Bz: benzoyl; CPS: capsular polysaccharide; DMF: N,N

Computational methods in drug discovery

• Sumudu P. Leelananda and
• Steffen Lindert

Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

• from a distantly-related structure has been used in the design of inhibitors for this structure [42]. Similarly, M antigen structure prediction by homology modeling has given insights into function by revealing that the structures and domains are similar to fungal catalases [43]. One of the pioneering

Automated glycan assembly of a S. pneumoniae serotype 3 CPS antigen

• Markus W. Weishaupt,
• Stefan Matthies,
• Mattan Hurevich,
• Claney L. Pereira,
• Heung Sik Hahm and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2016, 12, 1440–1446, doi:10.3762/bjoc.12.139

• using Pd(OH)2/C in methanol/water/acetic acid (50:25:1 v/v/v) afforded the fully deprotected S. pneumoniae serotype 3 CPS antigen 11 in 71% yield over three steps (Scheme 5). Conclusion The first automated glycan assembly of a conjugation-ready S. pneumoniae serotype 3 trisaccharide 11 using glucuronic

Elucidation of a masked repeating structure of the O-specific polysaccharide of the halotolerant soil bacteria Azospirillum halopraeferens Au4

• Elena N. Sigida,
• Yuliya P. Fedonenko,
• Alexander S. Shashkov,
• Nikolay P. Arbatsky,
• Evelina L. Zdorovenko,
• Svetlana A. Konnova,
• Vladimir V. Ignatov and
• Yuriy A. Knirel

Beilstein J. Org. Chem. 2016, 12, 636–642, doi:10.3762/bjoc.12.62

• chain (OPS) called O antigen and capsular polysaccharide (K antigen) of Azospirillum, which is an extracellular form of LPS [8][9], are important for the interaction between bacteria and host plants. The cell-surface polysaccharides of Azospirillum are involved in overcoming of unfavorable conditions

• , often non-stoichiometric, are not uncommon for Gram-negative bacteria. They occur independently of the polymerization mechanism [21][22] and often are associated with temperate bacteriophages that bear the corresponding transferases. Such alterations in certain O-antigen structures of emerging human

Impact of multivalent charge presentation on peptide–nanoparticle aggregation

• Daniel Schöne,
• Boris Schade,
• Christoph Böttcher and
• Beate Koksch

Beilstein J. Org. Chem. 2015, 11, 792–803, doi:10.3762/bjoc.11.89

• DNA can drive the assembly to form extended networks [19]. Although the relationship between the primary and quaternary structures of peptides and proteins are less clear than for DNA, protein-based recognition systems containing antigen–antibody [20], biotin–streptavidin [21], and peptide–peptide [22

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

• are quite homogeneous, we used these nanoparticles in cellular aggregation assays with galectin-1 and DU145 human prostate cancer cells. The DU145 cell line was chosen because it expresses a putative galectin-1 ligand – the Thomsen Friedenreich (TF) antigen on Mucin-1 [34][35]. As shown in Figure 7

• of glycoconjugates (TF antigen Mucin-1) on adjacent cells which directly facilitates aggregation; and (ii) clustering of receptors (TF antigen Mucin-1) which exposes adhesion molecules that interact with adhesion molecules on neighboring cells to cause aggregation. All four generations of the

Automated solid-phase synthesis of oligosaccharides containing sialic acids

• Chian-Hui Lai,
• Heung Sik Hahm,
• Chien-Fu Liang and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2015, 11, 617–621, doi:10.3762/bjoc.11.69

• carbohydrate antigens (TACAs) such as the sialyl-Tn antigen (sTn) [2]. Neu5Ac is often the terminal residue and is usually linked via an α-(2,3) or α-(2,6) linkage to galactose (Gal) (Figure 1) [3]. Automated glycan assembly enables rapid access to structurally defined oligosaccharides [4][5] including

• synthesis in the future as well. The tumor associated sTn carbohydrate antigen (Neu5Ac-α(2,6)GalNAc-α(1,1)linker) disaccharide 17, that resembles the sTn antigen glycan framework (Neu5Ac-α(2,6)GalNAc-α(1,1)Ser/Thr) was synthesized. In order to install the cis-glycoside formed by the union of the

• the tumour-associated antigen sialyl Tn (sTn). (a) FmocCl, py, CH2Cl2, rt, 4 h, 77%, (b) 2-chloroacetyl chloride, py, CH2Cl2, 0 °C to rt, 3 h, 88%, (c) HOPO(OBu)2, NIS, TfOH, 4 Å MS, CH3CN/CH2Cl2, −78 °C to 0 °C, 2 h, 80%. Automated synthesis of oligosaccharides with α(2,3)-, α(2,6)-sialic acid

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

• changes in glycosyltransferase activity and expression [8][9][10]. Furthermore, the prevalence of truncated saccharide antigens such as the Tn antigen [11], the Thomsen–Friedenreich (TF) antigen, and their sialylated congeners [8][9][10][12] leads to an insufficient shielding of the peptide backbone

• antibodies elicited from this vaccine were found to cross-react with native TF epitopes of MCF-7 cancer cells. Similarly, Yang et al. found that fluorinated sTn antigen conjugates were significantly more immunogenic than their natural congeners and also elicited antibodies cross-reactive to sTn-positive LS-C

• tumor cells [32]. In this context and as part of ongoing research devoted to the development of selectively fluorinated MUC1 glycopeptide-based vaccines, we report herein on the successful preparation of two novel MUC1 glycoconjugates comprising 4’-deoxy-4’-fluoro-TF antigen side chains in their B cell

Synthesis of the pentasaccharide repeating unit of the O-antigen of E. coli O117:K98:H4

• Pintu Kumar Mandal

Beilstein J. Org. Chem. 2014, 10, 2724–2728, doi:10.3762/bjoc.10.287

• Pintu Kumar Mandal Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram extension, Sitapur Road, Lucknow, 226 031, India 10.3762/bjoc.10.287 Abstract The pentasaccharide repeating unit of the O-antigen of E. coli O117:K98:H4 strain has

• coli; glycosylation; lipopolysaccharide; O-antigen; pentasaccharide; Introduction Escherichia coli becomes an important human pathogen in recent years owing to the emergence of new pathogenic strains [1]. Several diseases, such as meningitis and sepsis [2], diarrhoeal outbreaks [3] and urinary tract

• glycosylation strategy has been developed to synthesize a pentasaccharide 3-aminopropyl glycoside (1) corresponding to the O-antigen of E. coli O117:K98:H4 strain. The in situ removal of the PMB ether in one-pot following the glycosylation reaction reduced the overall number of steps. Structure of the