Recent Developments in Solid-Phase Glycan Synthesis

Huang, Jhih-Yi; Delbianco, Martina

doi:10.1055/a-1938-2293

Cited by 4 publications

(4 citation statements)

References 139 publications

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“…The oligosaccharides were prepared using a home-built synthesizer designed at the Max Planck Institute of Colloids and Interfaces 58 . All details concerning BB synthesis 75 , 76 , AGA modules 60 , 77 and post-AGA manipulations 78 can be found in Supplementary Sections 2 and 3 .…”

Section: Methodsmentioning

confidence: 99%

Synthesis of a glycan hairpin

et al. 2023

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The primary sequence of a biopolymer encodes the essential information for folding, permitting to carry out sophisticated functions. Inspired by natural biopolymers, peptide and nucleic acid sequences have been designed to adopt particular three-dimensional (3D) shapes and programmed to exert specific functions. In contrast, synthetic glycans capable of autonomously folding into defined 3D conformations have so far not been explored owing to their structural complexity and lack of design rules. Here we generate a glycan that adopts a stable secondary structure not present in nature, a glycan hairpin, by combining natural glycan motifs, stabilized by a non-conventional hydrogen bond and hydrophobic interactions. Automated glycan assembly enabled rapid access to synthetic analogues, including site-specific 13C-labelled ones, for nuclear magnetic resonance conformational analysis. Long-range inter-residue nuclear Overhauser effects unequivocally confirmed the folded conformation of the synthetic glycan hairpin. The capacity to control the 3D shape across the pool of available monosaccharides has the potential to afford more foldamer scaffolds with programmable properties and functions.

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Section: Methodsmentioning

confidence: 99%

Synthesis of a glycan hairpin

et al. 2023

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“…We prepared a collection of synthetic hairpin analogues to systematically analyze (i) the chemical structure of the turn unit, (ii) the interstrand interactions between the β-1,4-glucan strands, and (iii) the strands’ length influence on conformational stability (Figure ). All hairpin analogues were synthesized with automated glycan assembly (AGA) , ; the collection featured 13 C-labeled analogues , as well as a stapled glycan hairpin to serve as a “fully folded” reference structure . Structural analysis was performed with nuclear magnetic resonance (NMR) spectroscopy, assisted by molecular dynamics (MD) simulations.…”

Section: Introductionmentioning

confidence: 99%

Dissecting the Conformational Stability of a Glycan Hairpin

Yadav,

Djalali,

Poveda

et al. 2024

J. Am. Chem. Soc.

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Systematic structural studies of model oligopeptides revealed important aspects of protein folding and offered design principles to access non-natural materials. In the same way, the rules that regulate glycan folding could be established by studying synthetic oligosaccharide models. However, their analysis is often limited due to the synthetic and analytical complexity. By utilizing a glycan capable of spontaneously folding into a hairpin conformation as a model system, we investigated the factors that contribute to its conformational stability in aqueous solution. The modular design of the hairpin model featured a trisaccharide turn unit and two β-1,4-oligoglucoside stacking strands that allowed for systematic chemical modifications of the glycan sequence, including the introduction of NMR labels and staples. Nuclear magnetic resonance assisted by molecular dynamics simulations revealed that stereoelectronic effects and multiple glycan−glycan interactions are the major determinants of folding stabilization. Chemical modifications in the glycan primary sequence (e.g., strand elongation) can be employed to fine-tune the rigidity of structural motifs distant from the modification sites. These results could inspire the design of other glycan architectures, with implications in glycobiology and material sciences.

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“…Automated glycan assembly (AGA) has emerged as a versatile synthetic platform to rapidly obtain well-defined glycan oligomers . Following many synthetic and technological advances, some challenges such as the installation of certain monosaccharides (e.g., α-sialic acid) , and linkages (e.g., β-mannosides) remain. , While enzymatic installation of challenging monosaccharide residues on glycan backbones prepared by AGA could address some of these limitations, its scope remained bound to simple backbones lacking degenerative residues . An additional challenge often faced during post-AGA deprotection steps is the formation of ill-defined aggregates that dramatically decrease overall yields for glycans that are prone to aggregation …”

Section: Introductionmentioning

confidence: 99%

Phosphates as Assisting Groups in Glycan Synthesis

Sletten,

Fittolani,

Hribernik

et al. 2023

ACS Cent. Sci.

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In nature, phosphates are added to and cleaved from molecules to direct biological pathways. The concept was adapted to overcome limitations in the chemical synthesis of complex oligosaccharides. Phosphates were chemically placed on synthetic glycans to ensure sitespecific enzymatic elongation by sialylation. In addition, the deliberate placement of phosphates helped to solubilize and isolate aggregating glycans. Upon traceless removal of the phosphates by enzymatic treatment with alkaline phosphatase, the native glycan structure was revealed, and the assembly of glycan nanostructures was triggered.

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Recent Developments in Solid-Phase Glycan Synthesis

Cited by 4 publications

References 139 publications

Synthesis of a glycan hairpin

Synthesis of a glycan hairpin

Dissecting the Conformational Stability of a Glycan Hairpin

Phosphates as Assisting Groups in Glycan Synthesis

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