Long oligodeoxynucleotides: chemical synthesis, isolation via catching-by-polymerization, verification via sequencing, and gene expression demonstration

• Yipeng Yin,
• Reed Arneson,
• Alexander Apostle,
• Adikari M. D. N. Eriyagama,
• Komal Chillar,
• Emma Burke,
• Martina Jahfetson,
• Yinan Yuan and
• Shiyue Fang

Beilstein J. Org. Chem. 2023, 19, 1957–1965, doi:10.3762/bjoc.19.146

• engineering [3][4], mRNA vaccine [5], CRISPR/Cas9 genome editing [6], and DNA digital information storage [7] are constrained by the lack of affordable and high-quality long ODNs with no or little sequence restrictions and short turnaround time. Currently, long ODNs are mostly assembled using chemically

Cyclodextrins as building blocks for new materials

• Miriana Kfoury and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2023, 19, 889–891, doi:10.3762/bjoc.19.66

• containing CDs. Three clinical trials have demonstrated the use of CDs in the treatment of COVID-19. Two of them use the sulfobutyl ether β-CD/remdesivir inclusion complex and the third applies the α-CD/sulforaphane inclusion complex called Sulforadex® [6]. The approved Janssen vaccine against SARS-CoV-2

Insight into oral amphiphilic cyclodextrin nanoparticles for colorectal cancer: comprehensive mathematical model of drug release kinetic studies and antitumoral efficacy in 3D spheroid colon tumors

• Sedat Ünal,
• Gamze Varan,
• Juan M. Benito,
• Yeşim Aktaş and
• Erem Bilensoy

Beilstein J. Org. Chem. 2023, 19, 139–157, doi:10.3762/bjoc.19.14

• Sedat Unal Gamze Varan Juan M. Benito Yesim Aktas Erem Bilensoy Department of Pharmaceutical Technology, Faculty of Pharmacy, Erciyes University, 38280, Kayseri, Turkey Department of Vaccine Technology, Vaccine Institute, Hacettepe University, 06100, Ankara, Turkey Institute for Chemical Research

Preparation of β-cyclodextrin/polysaccharide foams using saponin

• Max Petitjean and
• José Ramón Isasi

Beilstein J. Org. Chem. 2023, 19, 78–88, doi:10.3762/bjoc.19.7

• coronavirus vaccine chitosan–saponin coatings have been developed to study its immunogenic potential [32]. A complexation between saponin and cyclodextrins (native or derivative) is possible [33], and the resulting release kinetics is appropriate for the creation of new saponin-based drugs [34]. Their

New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling

• Elenilson F. da Silva,
• Krist Helen Antunes Fernandes,
• Denise Diedrich,
• Jessica Gotardi,
• Marcia Silvana Freire Franco,
• Carlos Henrique Tomich de Paula da Silva,
• Ana Paula Duarte de Souza and
• Simone Cristina Baggio Gnoatto

Beilstein J. Org. Chem. 2022, 18, 1524–1531, doi:10.3762/bjoc.18.161

• forecast of increasing numbers of RSV infections in the future, and the medical requirements associated with severe RSV infections, no vaccine or effective drugs have been developed so far, which reinforces the urgency for the research and development of a new type of anti-RSV drugs that can be widely

Total synthesis of the O-antigen repeating unit of Providencia stuartii O49 serotype through linear and one-pot assemblies

• Tanmoy Halder and
• Somnath Yadav

Beilstein J. Org. Chem. 2021, 17, 2915–2921, doi:10.3762/bjoc.17.199

• stuartii is a class of enterobacteria of the family Providencia that is responsible for several antibiotic resistant infections, particularly urinary tract infections of patients with prolonged catheterization in hospital settings. Towards the goal of development of vaccine candidates against this pathogen

• . Structurally, the O-antigens consist of polysaccharide repeating units bearing several different monosaccharides. Due to their importance in regulating the host’s immune system, the bacterial cell surface LPS in general and the O-antigens in particular have been proposed and reported as candidates for vaccine

• ][20][21]. For the above purposes, large scale access to pure, defined, and homogeneous samples of the desired LPS oligosaccharides are essential for realization of the goal towards vaccine development against these pathogens [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21

Antiviral therapy in shrimp through plant virus VLP containing VP28 dsRNA against WSSV

• Santiago Ramos-Carreño,
• Ivone Giffard-Mena,
• Jose N. Zamudio-Ocadiz,
• Alfredo Nuñez-Rivera,
• Ricardo Valencia-Yañez,
• Jaime Ruiz-Garcia,
• Maria Teresa Viana and
• Ruben D. Cadena-Nava

Beilstein J. Org. Chem. 2021, 17, 1360–1373, doi:10.3762/bjoc.17.95

• treatment itself but the dose that finally reaches the shrimp tissues. An investigation will be conducted testing higher doses. Oral antiviral treatment in aquatic organisms is not straightforward because of the enormous challenges of breaking the water barrier. Therefore, for therapy or vaccine, it is

Synthesis of Streptococcus pneumoniae serotype 9V oligosaccharide antigens

• Sharavathi G. Parameswarappa,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2020, 16, 1693–1699, doi:10.3762/bjoc.16.140

• vaccines. The serotype 9V is part of the currently marketed conjugate vaccine and contains an acetate modification. To better understand the importance of glycan modifications in general and acetylation in particular, defined oligosaccharide antigens are needed for serological and immunological studies

• are still of growing concern due to an increase in non-vaccine serotypes and the cost of implementing these expensive vaccines in national immunization programs [4][5][6]. CPS is an important bacterial virulence factor and is critical for the interaction with the host as it helps the bacteria to

• polysaccharides are O-acetylated [9][10]. Especially SP serotypes, such as 9 (A, V) and 18C differ in O-acetylation. Two O-acetylated serotypes (9V and 18C) are part of the commercial vaccine Prevnar® 13. The traditional CPS isolation approach produces varying length CPS with different degrees of acetylation. An

Anthelmintic drug discovery: target identification, screening methods and the role of open science

• Frederick A. Partridge,
• Ruth Forman,
• Carole J. R. Bataille,
• Graham M. Wynne,
• Marina Nick,
• Angela J. Russell,
• Kathryn J. Else and
• David B. Sattelle

Beilstein J. Org. Chem. 2020, 16, 1203–1224, doi:10.3762/bjoc.16.105

• ][63][64][65]. A hookworm vaccine is at a more advanced stage of development [66] and a schistosomiasis vaccine is in a clinical Phase III trial [67], however, no vaccines are currently in use in the field. The current anthelmintic pipeline and the drug discovery landscape for parasitic helminth

• vaccine is available but the drug praziquantel (5) is an effective treatment. It is administered to children or whole communities often in mass drug administration (MDA) programmes [172]. An unfortunate drawback is that the drug is currently generated and administered as a racemic mixture. The pure active

Convenient synthesis of the pentasaccharide repeating unit corresponding to the cell wall O-antigen of Escherichia albertii O4

• Tapasi Manna,
• Arin Gucchait and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2020, 16, 106–110, doi:10.3762/bjoc.16.12

• . albertii O4 strain [11], which is a pentasaccharide comprising of α-linked ᴅ-galactosamine, β-linked ᴅ-glucosamine, β-linked ᴅ-galactose, α-linked ʟ-fucose and α-linked ʟ-rhamnose moieties. In the recent past, several vaccine candidates have been developed to control bacterial infections by conjugating

Chemical synthesis of the pentasaccharide repeating unit of the O-specific polysaccharide from Escherichia coli O132 in the form of its 2-aminoethyl glycoside

• Debasish Pal and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2019, 15, 2563–2568, doi:10.3762/bjoc.15.249

• important for the pathogenicity of the microorganisms [2]. Their antigenic character has made them attractive targets for designing potential vaccine candidates. Arguably these complex structures can be isolated from the biological sources, however, often this isolation is cumbersome and becomes too

• expensive to get reasonable quantities of material with adequate purity. Therefore, the chemical syntheses of these complex structures become the only option to afford the material for detailed biological studies leading to the exploration of the vaccine potential. Escherichia coli is a Gram-negative

• chemically synthesized oligosaccharides before [8][9][10]. The corresponding aminopropyl linker has also been used by others [11]. The chemically synthesized oligosaccharide structure will help to elucidate further biological implications of the O-antigen concerned and possible vaccine potential. Results and

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

• hindrance of the mannose and peptide part during the inclusion process of the adamantane [37][39]. It is well known that vaccine adjuvants can enhance or modulate the Th1/Th2-bias of an induced immune response. Interferon-γ (as a Th1 cytokine) and IL-4 (as a Th2 cytokine) induce isotype switching to IgG2a

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

• heroin vaccine, but exhibited attenuated protection against fentanyl compared to our fentanyl vaccine. Conclusion: After thorough investigation of this strategy, we have identified key considerations for the development of a chemically contiguous heroin–fentanyl vaccine. Importantly, this is the first

• report of such a strategy in the opioid–drug–vaccine field. Keywords: antinociception; fentanyl; hapten; heroin; vaccine; Introduction In 2016, the Centers for Disease Control (CDC) estimated that approximately 20.4% of the U.S. population (e.g., 50 million people) was suffering from chronic pain [1

• reducing overdose. By chemically attaching a non-immunogenic drug-like molecule to an immunogenic carrier protein, a vaccine is formed that has the capacity to stimulate an immune response, generating antibodies capable of binding the targeted drug. Moreover, when a user consumes the drug, the antibodies

Towards the preparation of synthetic outer membrane vesicle models with micromolar affinity to wheat germ agglutinin using a dialkyl thioglycoside

• Dimitri Fayolle,
• Nathalie Berthet,
• Bastien Doumeche,
• Olivier Renaudet,
• Peter Strazewski and
• Michele Fiore

Beilstein J. Org. Chem. 2019, 15, 937–946, doi:10.3762/bjoc.15.90

• membrane of Gram-negative bacteria, are considered today as attractive candidates for vaccine delivery. However, they have some disadvantages, they are not easy to produce and are difficult to characterize [2][3]. Moreover, toxic lipopolysaccharides (LPS) present in the outer membrane of most of Gram

• -negative bacteria [7] are challenges for the current research in the field. Artificial OMV, composed of synthetic and non-toxic, non-immunogenic phospholipids and glycolipids are good candidates for drug or vaccine delivery. One of the most common reactions used to prepare monoalkyl glycosides is the

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

• feasible targets for both parasite detection and vaccine development [3]. Leishmania, an obligate intracellular parasite with varying surface glycoconjugates, infects an estimated 12 million people worldwide and has 350 million people at risk in endemic areas (predominately in underdeveloped countries

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

• 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

• conjugate vaccine [33], and the synthesis of E. faecium wall teichoic acid fragments for vaccine development [34][35]. We have been interested in α-D-GalpNAc-(1-3)-β-D-GalpNAc as a part of our ongoing syntheses of S. pneumoniae lipoteichoic acid (LTA) derivatives [20][36][37]. During optimization of the

Synthetic avenues towards a tetrasaccharide related to Streptococcus pneumonia of serotype 6A

• Aritra Chaudhury,
• Mana Mohan Mukherjee and
• Rina Ghosh

Beilstein J. Org. Chem. 2018, 14, 1095–1102, doi:10.3762/bjoc.14.95

• conjugate in proper amounts for future vaccine development can only be met via chemical synthesis. Therefore, a number of syntheses targeting the SPn 6A tetrasaccharide has been reported in literature. Initial reports of a linear synthesis were made by Vliegenthart et al. in the nineties [17][18][19][20][21

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

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

• ). These lipid A variants are highly endotoxic and represent the most effective stimulators of the intracellular pro-inflammatory signaling. However, partial activation of the TLR4·MD-2 complex by certain lipid A substructures (such as 1-O-dephosphorylated Salmonella minnesota lipid A – a licenced vaccine

• vaccine adjuvants [59][60][61]. X-ray structural analyses of the MD-2∙TLR4 complexes with bound variably acylated lipid A uncovered markedly different modes of interaction of agonist and antagonist TLR4 ligands. Commonly, the binding of hexaacylated bisphosphorylated lipid A (such as lipid A from E. coli

• infection and persistent inflammation. 2.2. Synthesis of monophosphoryl lipid A (MPLA) as potential vaccine adjuvant In contrast to the attenuated or whole killed vaccines which contain bacterial cell wall components and nucleic acids serving as naturally occurring adjuvants, the subunit vaccines lack these

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

• the use of these self-glycans for the design of effective vaccine and inspired the preparation of new generation GAuNPs, coated with synthetic partial structures of Man9 multimerized on the same GAuNP, which provided better binding to the anti-HIV antibody 2G12 compared to GAuNPs carrying only one

• the saccharide. Finally, these results represent a solid support for the design of new and more effective nanoparticles based systems. A different approach towards the development of a synthetic HIV vaccine candidate based on GAuNPs, exploit the glyco-nanosystem as a tool which modulate and control

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

• polysaccharides (CPS) that surround them, are responsible for about 90% of infections worldwide [7]. The licensed polysaccharide vaccine Pneumovax 23 contains serotype 12F but is not efficacious in young children or elderly people, those at highest risk. The carbohydrate conjugate vaccines Prevanar13™ and

• with 85% [17]. In order to improve current glycoconjugate vaccines additional serotypes such as 12F should be included in next-generation preparations [18]. Synthetic oligosaccharides are important tools for the identification of vaccine epitopes and have been the key to the creation of monoclonal

• antibodies that serve as tools for vaccine design [19] and for the detection of pathogenic bacteria such as Bacillus anthracis [20][21]. S. pneumoniae 12F CPS consists of hexasaccharide repeating units containing the [→4)-α-L-FucpNAc-(1→3)-β-D-GalpNAc-(1→4)-β-D-ManpNAcA-(1→] polysaccharide backbone with a

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

• ; oligosaccharides; solid-phase synthesis; Streptococcus pneumoniae; Introduction The Gram-positive encapsulated commensal bacterium Streptococcus pneumoniae [1][2][3] can cause serious medical conditions like pneumonia, meningitis, endocarditis and sepsis [4]. S. pneumoniae is the leading cause of vaccine

• finally elucidated in 1941 [11], as being composed of repeating units of β-(1,3)-linked cellobiuronic acid (Figure 1). CPS plays a major role in S. pneumoniae virulence [12]. A commercial 17-valent polysaccharide vaccine was introduced in 1977, followed by a 23-valent vaccine in 1983 [13][14][15

• ]. Serotype 3 of S. pneumoniae is one of the most prevalent serotypes causing acute otitis media [16] and is one of the thirteen serotypes included in the blockbuster pneumococcal conjugate vaccine Prevnar 13® [17][18]. Vaccines against S. pneumoniae are usually manufactured using isolated CPS structures

Three new trixane glycosides obtained from the leaves of Jungia sellowii Less. using centrifugal partition chromatography

• Luíse Azevedo,
• Larissa Faqueti,
• Marina Kritsanida,
• Antonia Efstathiou,
• Despina Smirlis,
• Gilberto C. Franchi Jr,
• Grégory Genta-Jouve,
• Sylvie Michel,
• Louis P. Sandjo,
• Raphaël Grougnet and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2016, 12, 674–683, doi:10.3762/bjoc.12.68

• artemisinine, thapsigargin, and parthenolide are used nowadays for the treatment of malaria and cancer and have shown antileishmanial activities [13][14]. About two million new cases of Leishmania infection are considered to occur every year in tropical countries including Brazil. Today no effective vaccine

N-Alkyl derivatives of diosgenyl 2-amino-2-deoxy-β-D-glucopyranoside; synthesis and antimicrobial activity

• Agata Walczewska,
• Daria Grzywacz,
• Dorota Bednarczyk,
• Małgorzata Dawgul,
• Andrzej Nowacki,
• Wojciech Kamysz,
• Beata Liberek and
• Henryk Myszka

Beilstein J. Org. Chem. 2015, 11, 869–874, doi:10.3762/bjoc.11.97

• used as detergents, surfactants and emulsifiers. Moreover, they display a wide range of pharmacological activities, including antifungal, antiparasitic, antiinflammatory, antibacterial, and antitumor activities [2][3][4][5]. No wonder, saponins have been evaluated as vaccine adjuvants [6]. Despite the

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

• prevention and cure. Thus, administration of a therapeutic vaccine will trigger an effective immune response to allow eradication of tumor cells, which might have evaded surgery or have metastasized into the bloodstream [5]. A prerequisite for this approach is inter alia an efficient distinction of malignant

• 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

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

• information to other cell types lead to the notion that different subtypes and subsets of DC are central regulators of both innate and adaptive immunity and thus they can also be harnessed for vaccine development [33] and also for immunotherapeutic interventions [34]. By using high throughput approaches we