Chemical approaches towards installation of rare functional groups in bacterial surface glycans

Qin, Chunjun; Ding, Mei-Ru; Tian, Guangzong; Zou, Xiang; Fu, Junjie; Hu, Jing; Yin, Jian

doi:10.1016/s1875-5364(22)60177-8

Cited by 6 publications

(7 citation statements)

References 231 publications

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“…The 2-acetamido-4-amino-D-fucose was first observed in the O-antigen of S. sonnei as a key residue and always occurs with the free amino group at the C-4 position [26]. The amino sugars' amino group is usually acetylated and formylated; however, acetimidoyl has also been identified in various bacterial glycans [27]. Moreover, amino acids are one of the most important substituents of amino sugars.…”

Section: O-modified Groupsmentioning

confidence: 99%

Effect of Side-Chain Functional Groups in the Immunogenicity of Bacterial Surface Glycans

Tian,

Qin,

et al. 2023

Molecules

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Glycans on the surface of bacteria have diverse and essential biological functions and have widely been employed for treating various bacterial infectious diseases. Furthermore, these glycans comprise various functional groups, such as O-, N-, and carboxyl-modified, which significantly increase the diversity of glycan structures. These functional groups are not only crucial for glycans’ structural identity but are also essential for their biological functions. Therefore, a clear understanding of the biological functions of these modified groups in corresponding bacterial glycans is crucial for their medical applications. Thus far, the activities of functional groups in some biomedical active carbohydrates have been elucidated. It has been shown that some functional groups are key constituents of biologically active bacterial glycans, while others are actually not essential and may even mask the functions of the glycans. This paper reviews the structures of naturally occurring side-chain functional groups in glycans located on the bacterial surface and their roles in immunological responses.

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Section: O-modified Groupsmentioning

confidence: 99%

Effect of Side-Chain Functional Groups in the Immunogenicity of Bacterial Surface Glycans

Tian,

Qin,

et al. 2023

Molecules

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“…8 Since key epitopes may be altered and labile substitutions may not survive the process of polysaccharide isolation, well- defined synthetic oligosaccharides have been invaluable tools to the growing field of glycoconjugate vaccine development. 19,20 Oligosaccharides corresponding to the O-antigens of S. dysenteriae serotypes 1, 21,22 3, 23 4, 24,25 5, 26 and 8, 27 S. flexneri serotypes 1, 28 2, 29 3, 30,31 4, 32 5, 33 and 6 34 as well as S. sonnei 35,36 44 In the course of our studies directed toward the synthetic carbohydrate-based antibacterial vaccine, we are particularly concerned about the roles of various functional groups in immunological activities of bacterial glycans. 44−47 Synthetic fragments and analogues corresponding to glycans form an important basis for elucidating their roles and key epitopes in physiological activities.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Only a few 3,4- O -pyruvyl ketal-modified d -galactoses and l -rhamnoses have been found. 2,3- O -Pyruvyl ketal has only been reported to modify β- d -glucuronic acids and α- d -galactoses in a few glycans . In the course of our studies directed toward the synthetic carbohydrate-based antibacterial vaccine, we are particularly concerned about the roles of various functional groups in immunological activities of bacterial glycans. − Synthetic fragments and analogues corresponding to glycans form an important basis for elucidating their roles and key epitopes in physiological activities.…”

Section: Introductionmentioning

confidence: 99%

“…2,3- O -Pyruvyl ketal has only been reported to modify β- d -glucuronic acids and α- d -galactoses in a few glycans . In the course of our studies directed toward the synthetic carbohydrate-based antibacterial vaccine, we are particularly concerned about the roles of various functional groups in immunological activities of bacterial glycans. − Synthetic fragments and analogues corresponding to glycans form an important basis for elucidating their roles and key epitopes in physiological activities. Intense efforts have been devoted for the introduction of a pyruvyl ketal to carbohydrates, including acid-catalyzed ketalation with pyruvate , or pyruvate dialkyl dithioketal, ,− and oxidative formation of a carboxyl moiety in a ketal precursor. − These methods have facilitated the syntheses of important bacterial glycans, including the capsular polysaccharide (CPS) of E.…”

Section: Introductionmentioning

confidence: 99%

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Chemical Synthesis and Antigenicity Evaluation of Shigella dysenteriae Serotype 10 O-Antigen Tetrasaccharide Containing a (S)-4,6-O-Pyruvyl Ketal

Qin

Tian

et al. 2022

J. Am. Chem. Soc.

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Shigella is the second most common etiologic pathogen responsible for childhood acute diarrhea. An anti-Shigella vaccine is still eagerly awaited due to the increasing drug resistance of this pathogen. The Shigella O-antigen is a promising vaccine target. To identify the immune epitopes of the glycan, the first total synthesis of Shigella dysenteriae serotype 10 O-antigen tetrasaccharide containing a (S)-4,6-O-pyruvyl ketal was completed. The 1,2-trans-β-glycosylation & C2 epimerization and conformational locking strategies facilitated the construction of two 1,2-cis-β-glycosidic linkages. The reactivities of both the glycosyl donor and acceptor were improved by adding electron-donating benzyl groups, enabling an efficient assembly of the tetrasaccharide. The (S)-4,6-Opyruvyl ketal was introduced at the final stage due to its influence on the glycosylation stereospecificity and efficiency. In addition, (R)-4,6-O-pyruvylated and nonpyruvylated tetrasaccharides and three further fragments were synthesized. Glycan microarray screening revealed that the tetrasaccharide repeating unit is the key antigenic epitope of the O-antigen. Moreover, the (S)-4,6-O-pyruvyl ketal is an essential structural feature of this antigen for designing carbohydrate-based vaccines against S. dysenteriae serotype 10. The comparison of the (S)-4,6-O-pyruvylated glycan and its (R)-epimer will set an example for biological evaluation of other bacterial glycans containing pyruvyl ketals.

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“…Focusing on the aminodisaccharide fragment [→4)-β- d -Glc p N(propanoyl)3N(formyl)AN-(1→3)-β- d -Fuc p NAc4N-(1→], there are five amino groups with five different modifications, including carboxamidation, free amine, acetylation, formylation, and propanoylation. Highly functionalized synthetic disaccharide is thought to be essential for investigating the structure–activity relationship of this structurally unique bacterial glycan . The AAT building blocks have been synthesized from d -glucosamine via nucleophilic substitution and C6 deoxygenation, from l -threonine via de novo assembly, from d -glucal via azidonitration and intramolecular displacement, and from d -rhamnose via one-pot sequential inversion .…”

mentioning

confidence: 99%

Chemical Synthesis of a Densely Functionalized Aminodisaccharide from Fusobacterium nucleatum ATCC 23726 O-Antigen

Ding,

Qin,

Sun

et al. 2024

Org. Lett.

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Fusobacterium nucleatum, a colorectal-cancer-associated oncomicrobe, can trigger or accelerate numerous pathologies. We report the first synthesis of a conjugation-ready disaccharide containing six amino groups from F. nucleatum ATCC 23726 O-antigen. Rare 2,3-diamido-D-glucuronic acid amide and 2acetamido-4-amino-D-fucose were synthesized from D-glucosamine through configuration inversion, nucleophilic substitution, C6 oxidation, and C6 deoxygenation. A judicious choice of protecting groups and reaction conditions enabled the selective installation of N-acetyl, N-propanoyl, N-formyl, and carboxamido groups.

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Chemical approaches towards installation of rare functional groups in bacterial surface glycans

Cited by 6 publications

References 231 publications

Effect of Side-Chain Functional Groups in the Immunogenicity of Bacterial Surface Glycans

Effect of Side-Chain Functional Groups in the Immunogenicity of Bacterial Surface Glycans

Chemical Synthesis and Antigenicity Evaluation of Shigella dysenteriae Serotype 10 O-Antigen Tetrasaccharide Containing a (S)-4,6-O-Pyruvyl Ketal

Chemical Synthesis of a Densely Functionalized Aminodisaccharide from Fusobacterium nucleatum ATCC 23726 O-Antigen

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