Expedited synthesis of mannose-6-phosphate containing oligosaccharides

Sletten, Eric T.; Danglad‐Flores, José; Leichnitz, Sabrina; Joseph, A. Abragam; Seeberger, Peter H.

doi:10.1016/j.carres.2021.108489

Cited by 13 publications

(14 citation statements)

References 19 publications

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“…Further advances in the synthesis of complex bacterial glycans will allow the faster generation of more and more complex glycans, making carbohydrate antigen production faster and more scalable. , Key challenges include not only further optimization of stereoselective glycosylation methodology and automated synthesis techniques (a technique that, if sufficiently matured, will also ensure reproducibility of oligosaccharide synthesis) but also the incorporation of functional groups, including labile esters, differently functionalized amines/amides, pyruvate ketals, and phosphates and phosphonates, which often provide microheterogeneity to the bacterial polysaccharide chains . A clear advantage of organic synthesis is the improvement of specific properties of the glycans, such as stability (as shown above for carbaMenA, Hib, and ST5 pneumococcal analogues).…”

Section: Discussionmentioning

confidence: 99%

“…71,420 Key challenges include not only further optimization of stereoselective glycosylation methodology and automated synthesis techniques (a technique that, if sufficiently matured, will also ensure reproducibility of oligosaccharide synthesis) but also the incorporation of functional groups, including labile esters, differently functionalized amines/amides, pyruvate ketals, and phosphates and phosphonates, which often provide microheterogeneity to the bacterial polysaccharide chains. 421 A clear advantage of organic synthesis is the improvement of specific properties of the glycans, such as stability (as shown above for carbaMenA, 126 Hib, 87 and ST5 158 pneumococcal analogues). In some examples, chemically derived structures have the potential to improve the vaccine design for those polysaccharides that have been proven less efficacious in humans (e.g.…”

Section: Aementioning

confidence: 99%

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Synthetic Glycans to Improve Current Glycoconjugate Vaccines and Fight Antimicrobial Resistance

Bino

Østerlid

et al. 2022

Chem. Rev.

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Antimicrobial resistance (AMR) is emerging as the next potential pandemic. Different microorganisms, including the bacteria Acinetobacter baumannii, Clostridioides diff icile, Escherichia coli, Enterococcus faecium, Klebsiella pneumoniae, Neisseria gonorrhoeae, Pseudomonas aeruginosa, non-typhoidal Salmonella, and Staphylococcus aureus, and the fungus Candida auris, have been identified by the WHO and CDC as urgent or serious AMR threats. Others, such as group A and B Streptococci, are classified as concerning threats. Glycoconjugate vaccines have been demonstrated to be an efficacious and cost-effective measure to combat infections against Haemophilus inf luenzae, Neisseria meningitis, Streptococcus pneumoniae, and, more recently, Salmonella typhi. Recent times have seen enormous progress in methodologies for the assembly of complex glycans and glycoconjugates, with developments in synthetic, chemoenzymatic, and glycoengineering methodologies. This review analyzes the advancement of glycoconjugate vaccines based on synthetic carbohydrates to improve existing vaccines and identify novel candidates to combat AMR. Through this literature survey we built an overview of structure−immunogenicity relationships from available data and identify gaps and areas for further research to better exploit the peculiar role of carbohydrates as vaccine targets and create the next generation of synthetic carbohydrate-based vaccines.

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Section: Discussionmentioning

confidence: 99%

Section: Aementioning

confidence: 99%

Synthetic Glycans to Improve Current Glycoconjugate Vaccines and Fight Antimicrobial Resistance

Bino

Østerlid

et al. 2022

Chem. Rev.

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“…The synthesis of complex ionic glycans has represented the Holy Grail for carbohydrate chemists. Procedures to introduce some ionic modifications in SPGS have been reported, 54,90,92 but many more targets should be produced to confirm the applicability of these approaches. These syntheses suffer from the amphiphilic nature of partially protected intermediates and their tendency to aggregate and precipitate out of solution.…”

Section: Discussionmentioning

confidence: 99%

“…On-resin phosphorylation was developed to access mannose-6-phosphate (M6P)-containing oligosaccharides (Scheme 11 ). 92 Diphenyl phosphoryl chloride was selected as the phosphorylating agent (in CH 2 Cl 2 with 10% pyridine), requiring no further oxidation or extra activation as in phosphoramidate and H-phosphonate chemistries. This protocol generated a fully protected uncharged glycan, easing purification and handling.…”

Section: Solid-phase Glycan Synthesismentioning

confidence: 99%

Recent Developments in Solid-Phase Glycan Synthesis

Huang

Delbianco

2022

Synthesis

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Solid-phase glycans synthesis (SPGS) is a valuable approach to access broad collections of complex, well-defined oligo- and polysaccharides in short amount of time. The target structure is assembled following iterative cycles of glycosylation and deprotection, often aided by automated machines. To expand the scope of SPGS, new solid supports, linkers, glycosylation and deprotection reactions, and functionalization strategies are constantly being developed. Here we discuss the state of the art of SPGS, with particular focus on the chemistry happening on solid-phase. We highlight recent achievements as well as challenges to be addressed to expand the scope of SPGS even further.

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“…[ 46 ] Besides the sulfated glycans, the phosphorylated glycans were also synthesized by AGA in a rapid manner. [ 47 ]…”

Section: Automated Glycan Assemblymentioning

confidence: 99%

Automated Chemical Solid‐Phase Synthesis of Glycans

Yang

2022

Chin. J. Chem.

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Automated chemical solid-phase synthesis is an automation platform for rapid and reliable synthesis of glycans. Since the seminal work of Automated Glycan Assembly (AGA) disclosed by Seeberger in 2001, AGA has evolved from a proof-of-concept to a robust and reliable technology for streamlined production of various types of glycans. Through more than 20 years of unceasing efforts, the major breakthroughs in AGA including linkers, approved building blocks, and synthesizers have been acquired, and numerous influential achievements have been made in complex glycan synthesis. In addition, the HPLC-assisted automated synthesis emerges as a promising automation platform to access glycans. In this review, we highlight the key advances in the field of automated chemical solid-phase synthesis, especially in AGA. The synthesis of representative glycans based on AGA is also described.

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Expedited synthesis of mannose-6-phosphate containing oligosaccharides

Cited by 13 publications

References 19 publications

Synthetic Glycans to Improve Current Glycoconjugate Vaccines and Fight Antimicrobial Resistance

Synthetic Glycans to Improve Current Glycoconjugate Vaccines and Fight Antimicrobial Resistance

Recent Developments in Solid-Phase Glycan Synthesis

Automated Chemical Solid‐Phase Synthesis of Glycans

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