The role of chemistry in the success of oligonucleotides as therapeutics

• Pawan Kumar and
• Tom Brown

Beilstein J. Org. Chem. 2022, 18, 197–199, doi:10.3762/bjoc.18.22

• effective in patisiran, the first RNAi drug to reach patients. Lipid nanoparticles are also being used in the new generation of RNA vaccines for tackling the COVID pandemic. Another noteworthy advancement is the ease and scale with which oligonucleotides are being produced today. Without access to larger

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

• Tanmoy Halder Somnath Yadav Department of Chemistry, Indian Institute of Technology (ISM), Dhanbad, 826004, Jharkhand, India 10.3762/bjoc.17.199 Abstract Capsular polysaccharides of pathogenic bacteria have been reported to be effective vaccines against diseases caused by them. Providencia

• was then deprotected and N-acetylated to finally afford the desired trisaccharide repeating unit as its α-p-methoxyphenyl glycoside. Keywords: capsular polysaccharide; carbohydrate vaccines; O-antigen; oligosaccharide synthesis; one-pot synthesis; Introduction O-antigens or O-specific

• development [1][2][3][4][5][6][7][8]. This objective has been proposed to be achieved by the synthesis of chemically homogeneous glycoconjugates bearing the O-antigen oligosaccharide conjugated to peptides for eliciting the desired immune response through vaccines [9][10][11][12][13][14][15][16][17][18][19

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

• control [7]. So far several strategies have been reported to control the WSSV, including activation of the immune system, DNA vaccines, herbal extracts, and RNA interference (RNAi) [8][9]. Among them, the RNAi technology has shown great potential to protect shrimp against the WSSV in some lab-scale

• virus. It is imperative to find prevention that works. Vaccines or antiviral therapies to effectively control or eliminate these outbreaks should be a priority in further investigations. The Government and private sector should work together to develop strategies to protect the profitability of the

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• -driven vaccines and therapeutics, including two RNA-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines [46], as well as an siRNA–LNP for the treatment of a transthyretin amyloidosis [36]. However, further improvements in toxicity profiles, cargo delivery, and cell or organ

DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

• Yongdong Su,
• Maitsetseg Bayarjargal,
• Tracy K. Hale and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2021, 17, 749–761, doi:10.3762/bjoc.17.65

• +{FAM} ON and it was only present in the cytoplasm. These results indicate that ONs with phosphate modifications such as N+ or Ts might be suitable tools for the application of DNA and RNA vaccines [60], for the treatment of cancer [61], infectious diseases [62], and neurological disorders [63

Synthesis of monophosphorylated lipid A precursors using 2-naphthylmethyl ether as a protecting group

• Jundi Xue,
• Ziyi Han,
• Gen Li,
• Khalisha A. Emmanuel,
• Cynthia L. McManus,
• Qiang Sui,
• Dongmian Ge,
• Qi Gao and
• Li Cai

Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162

• might harness these immunostimulatory effects are particularly valuable as they can provide basis for the development of vaccines and adjuvants. For example, recent studies have disclosed that both the fatty acid structure and the phosphorylation degree can affect the activity and endotoxic effects [7

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

• . Here, we demonstrate a convergent [2 + 3] synthetic strategy to prepare the pentasaccharide repeating unit of 9V with and without an acetate group at the C-6 position of mannosamine. Keywords: antigen; carbohydrate chemistry; oligosaccharide; Streptococcus pneumoniae; vaccines; Introduction

• developing countries [3]. With increasing antimicrobial resistance to antibiotics, vaccines are becoming even more important to control these pathogens. Despite the availability of multivalent polysaccharide and glycoconjugate vaccines such as Pneumovax, Prevnar® 13, and Synflorix, pneumonococcal diseases

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

• I safety trials have been completed (NCT03383614). The management and control of the STHs, schistosomes and filarial parasites relies primarily on chemotherapy and education. Whilst vaccines are being developed for roundworms and whipworms, the development is still at the pre-clinical stage [61][62

• ][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

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• . Incorporation of fluorinated aromatic amino acids into proteins increases their catabolic stability especially in therapeutic proteins and peptide-based vaccines. This review seeks to summarize the different synthetic approaches in the literature to prepare ᴅ- or ʟ-fluorinated phenylalanines and their

• , especially in therapeutic proteins and peptide-based vaccines [18]. Enhanced catabolic stability [6] can arise from the role of particular aromatic amino acids in membrane–protein interactions [19]. Furthermore, fluorinated aromatic amino acids can alter enzymatic activity as a result of enhanced protein

• and activity of peptides in therapeutic vaccines and enzymes has been studied [19][26][27][28][29][30][31][32][33]. In this review we provide an overview for the various syntheses of FPhes and analogues. Five different categories of FPhe are represented and are classified I–V according to the position

Synthesis of new asparagine-based glycopeptides for future scanning tunneling microscopy investigations

• Laura Sršan and
• Thomas Ziegler

Beilstein J. Org. Chem. 2020, 16, 888–894, doi:10.3762/bjoc.16.80

• example, in anti-HIV therapy, MUC1-based antitumor vaccines, or as antibiotics [12][13][14]. Especially glycans bearing noncanonical amino acids, which can only be introduced into a peptide by organic synthesis, are suitable for cancer therapy since they show better resistance to enzymatic degradation in

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

• cell wall polysaccharides with suitable proteins, which include vaccines against Haemophilia influenza type b (Hib) [12][13], meningitis [14], pneumococcal infections [15][16] and enteric diseases such as cholera [17], diarrhea [18] and urinary tract infections [19]. Despite the possibility of

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

• mammalian hosts and therefore have been extensively studied as possible adjuvants for vaccines. Peptidoglycan is a polymeric component of the Gram-positive and Gram-negative bacterial cell wall. Breakdown products of polymeric peptidoglycan are called muropeptides. Muropeptides act as agonists of pathogen

• and leads to development of new approaches for the design of novel vaccines. Application of multi-PRR activation approaches can increase the immunity significantly [47]. Another example of dual adjuvant system is represented by the activation of dendritic cells via combined macrophage-inducible CLR

• applicable as an adjuvant for vaccines. Peptidoglycan fragments with immunostimulating properties. Immunostimulating mannosylated desmuramyl peptide (ManAdTP). General structure of: a) glycolyl and b) (R)-hydroxyisobutyryl derivatives. The effect of mannosyl desmuramyl peptides on production of anti-OVA IgG

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

• States has necessitated the development of new strategies to treat addiction. Monoclonal antibodies and antidrug vaccines provide a tool that both aids addiction management and reduces the potential for overdose. Dual drug vaccines formulated by successive conjugation or by mixture have certain drawbacks

• . The current study examines an approach for combatting the dangers of fentanyl-laced heroin, by using a hapten with one epitope that has domains for both fentanyl and heroin. Results: We evaluated a series of nine vaccines developed from chemically contiguous haptens composed of both heroin- and

• fentanyl-like domains. Analysis of the results obtained by SPR and ELISA revealed trends in antibody affinity and titers for heroin and fentanyl based on epitope size and linker location. In antinociception studies, the best performing vaccines offered comparable protection against heroin as our benchmark

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

• vesicles, alone or in mixture with phospholipids, mimicking bacterial outer membrane vesicles (OMV) with potential antiadhesive properties. Keywords: glycolipids; outer membrane vesicles; synthetic vaccines; Introduction Outer membrane vesicles (OMV) [1], lipid bilayer vesicles released from the outer

• -negative bacteria prevent the medical use of OMV from natural sources [4]. Licensed vaccines based on crude OMV are currently available to contribute to the prevention and to control at least twenty-five infections including pulmonary ones [5]. Developing synthetic vaccines against cancer [6][7] or Gram

• addition to its high efficiency and selectivity, the TEC reaction does not require any metal, a key feature for the preparation of potential vaccines. Results and Discussion Preparation of alkyl glycosides from unprotected sugars and lipophilic scaffolds Thioglycolipids are not native in OMV [1], but

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

• each year in predominately underdeveloped countries. The treatment of the disease is severely underdeveloped due to the ability of the Leishmania pathogen to evade and abate immune responses. In an effort to develop anti-leishmaniasis vaccines and adjuvants, novel carbohydrate-based probes were made to

• are no approved anti-leishmanial vaccines and the current therapeutics are toxic, expensive and prone to induce resistance, such as, amphotericin B (AmB), paromomycin and antimony-based chemotherapeutics [7][8][9]. With growing resistance to antileishmanial drugs and poor patient compliance, the

• development of safe, efficacious and inexpensive alternatives to current therapeutics is needed. Understanding the mechanisms by which Leishmania regulates host immune responses are crucial for the development of vaccines, which may induce adaptive immunity that may prove beneficial for combating other

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

• Shigella dysenteriae [23], as derivatives of the mucin O-glycan core structures for glycosidase studies [24], for the synthesis of T-antigen analogues [25], for the synthesis of E. coli O-antigens [26][27][28][29], for the development of Burkholderia vaccines [30][31][32], for the synthesis of PS A1

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

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

• ; oligosaccharides; stereoselectivity; total synthesis; Introduction Complex glycans serve as attractive targets for carbohydrate-based vaccines and therapeutics [1][2][3]. Streptococcus pneumonia (SPn) has been posing a serious threat in recent times. It is a major cause of pneumonia, bacteraemia, and meningitis

• SPn 6A in multicomponent vaccines like Pneumovax® has been recognized [15]. The low hydrolytic stability of the phosphodiester linkages in the clinical isolates of the SPn 6A polysaccharides poses a major drawback as it leads to low bioavailability [16]. Hence, the requirements of pure SPn 6A

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

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

• 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

• components. In the last decade much attention has been focused on the development of adjuvants that can render subunit vaccines more efficient by boosting the adaptive immune response. In this respect, TLR agonists deserved special consideration, since the induction of the innate immune signaling with PAMPs

• study demonstrated that both TLR4 and MyD88 signaling have a significant effect on the adaptive immune responses in MPLA-adjuvanted vaccines [105]. To gain deeper understanding of the mechanisms underlying beneficial non-toxic immune response induced by MPLA and to reveal the major structural

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

• glycopeptides (the alkyne source was propargylglycine in the peptide sequence) which have potential in synthetic vaccines [87][88] in moderate yields (30–47%) [85]. Once again these conditions take place under mild wet conditions, further underscoring the potential of this method. Due to the mild nature of DMC

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

• -based approach, which aim to trigger the production of specific and functional antibodies that prevent initial infection limiting pathogen/viral dissemination. Recent publications suggest that many different aspects are becoming clear and have to be underlined. The design of anti HIV-1 vaccines depends

• -glycopeptide antigens were able to stimulate the immune system, suggesting GAuNPs are interesting platforms for developing new immunotherapeutics. The potential of AuNPs as antigen carriers for the development of synthetic vaccines is still being investigated in the context of bacterial infections. NPs are

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

• Deutschland GmbH, Magnusstrasse 11, 12489 Berlin, Germany 10.3762/bjoc.13.19 Abstract The Gram-positive bacterium Streptococcus pneumoniae causes severe disease globally. Vaccines that prevent S. pneumoniae infections induce antibodies against epitopes within the bacterial capsular polysaccharide (CPS). A

• vaccines is the assembly of the trisaccharide β-D-GalpNAc-(1→4)-[α-D-Glcp-(1→3)]-β-D-ManpNAcA, in which the branching points are equipped with orthogonal protecting groups. A linear approach relying on the sequential assembly of monosaccharide building blocks proved superior to a convergent [3 + 3

• 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

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

• Berlin, Arnimallee 22, 14195 Berlin, Germany 10.3762/bjoc.12.139 Abstract Vaccines against S. pneumoniae, one of the most prevalent bacterial infections causing severe disease, rely on isolated capsular polysaccharide (CPS) that are conjugated to proteins. Such isolates contain a heterogeneous

• ]. 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

• conclusion, we have developed an efficient method for the synthesis of S. pneumoniae serotype 3 CPS structures. The products of these syntheses are currently used in the development of synthetic carbohydrate conjugate vaccines. Disaccharide repeating unit of the S. pneumoniae serotype 3 CPS. Building blocks

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

• the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, Geb. 708, D-55101 Mainz, Germany 10.3762/bjoc.11.15 Abstract The development of selective anticancer vaccines that provide enhanced protection against tumor recurrence and metastasis has been the subject of intense research in the

• to rapid in vivo degradation. To overcome these drawbacks, novel fluorinated MUC1 glycopeptide-BSA/TTox conjugate vaccines have been prepared. Immunization of mice with the 4’F-TF-MUC1-TTox conjugate resulted in strong immune responses overriding the natural tolerance against MUC1 and producing

• , which becomes accessible to the immune system and can be used as an additional immunogenic determinant for carbohydrate-based cancer vaccines [13]. Despite encouraging results with two- and three-component MUC1 conjugate vaccines in mice models [14][15][16][17][18][19][20][21][22][23][24][25], immune

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

• Laura Morelli Damiano Cancogni Marta Tontini Alberto Nilo Sara Filippini Paolo Costantino Maria Rosaria Romano Francesco Berti Roberto Adamo Luigi Lay Dipartimento di Chimica and ISTM-CNR, Universita degli Studi di Milano, via Golgi 19, I-20133 Milano, Italy Novartis Vaccines, Via Fiorentina 1

• ; vaccines; Introduction Neisseria meningitidis is an encapsulated, aerobic gram-negative diplococcus which causes significant morbidity and mortality in newborns, children and young adults worldwide through meningitis and/or septicemia. Although sporadic cases occur in Europe and North America, major

• conjugate vaccine [14]. Undoubtedly the recent increase of MenX infections has led to take in consideration this emerging serogroup for the development of new meningococcal vaccines [15][16]. Recently it has been reported that coupling long chain oligosaccharides from MenX CPS to the nontoxic mutant of