Comparison of the anti-amyloidogenic effect of O-mannosylation, O-galactosylation, and O-GalNAc glycosylation

Chen, Lin; Chen, Hsin‐Liang; Li, Yen-Li; Hsu, Ruei‐Lin; Luh, Frederick Y.; Yang, Lijun; Chou, Chia-Fu; Huang, Li-De; Lin, Chun‐Cheng; Chen, Rita P.‐Y.

doi:10.1016/j.carres.2014.01.025

Cited by 14 publications

(10 citation statements)

References 35 publications

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“…The effects of a large number of other modifications on physical stability have also been reported including different glycosylations [163] and fatty acid conjugation [164].…”

Section: Chemical Modificationsmentioning

confidence: 99%

Factors affecting the physical stability (aggregation) of peptide therapeutics

Zapadka

Becher

Santos³

et al. 2017

Interface Focus.

264

207

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The number of biological therapeutic agents in the clinic and development pipeline has increased dramatically over the last decade and the number will undoubtedly continue to increase in the coming years. Despite this fact, there are considerable challenges in the development, production and formulation of such biologics particularly with respect to their physical stabilities. There are many cases where self-association to form either amorphous aggregates or highly structured fibrillar species limits their use. Here, we review the numerous factors that influence the physical stability of peptides including both intrinsic and external factors, wherever possible illustrating these with examples that are of therapeutic interest. The effects of sequence, concentration, pH, net charge, excipients, chemical degradation and modification, surfaces and interfaces, and impurities are all discussed. In addition, the effects of physical parameters such as pressure, temperature, agitation and lyophilization are described. We provide an overview of the structures of aggregates formed, as well as our current knowledge of the mechanisms for their formation.

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“…The effects of a large number of other modifications on physical stability have also been reported including different glycosylations [163] and fatty acid conjugation [164].…”

Section: Chemical Modificationsmentioning

confidence: 99%

Factors affecting the physical stability (aggregation) of peptide therapeutics

Zapadka

Becher

Santos³

et al. 2017

Interface Focus.

264

207

View full text Add to dashboard Cite

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“…Glycosylation can enhance the molecular stability and change the conformation of the peptide backbone 57–59. Lin et al showed that the modification of hamster prion peptide with different sugar entities, such as mannose, galactose, and N-acetylgalactosamine (GalNAc), exerts diverse impacts on the conformational properties of the polypeptide chain.…”

Section: Glycosylation Strategy For Peptide Deliverymentioning

confidence: 99%

“…Lin et al showed that the modification of hamster prion peptide with different sugar entities, such as mannose, galactose, and N-acetylgalactosamine (GalNAc), exerts diverse impacts on the conformational properties of the polypeptide chain. Mannosylation of the prion exerted an inhibitory impact on the formation of amyloid fibril (a type of aggregation), implying an anti-aggregation function of this sugar entity on the prion peptide 59. It has been shown that the position of the glycosyl unit in the peptide's structure is an important factor in changing the conformation of the peptide backbone and may affect the biological properties of the modified peptide.…”

Section: Glycosylation Strategy For Peptide Deliverymentioning

confidence: 99%

Glycosylation, an effective synthetic strategy to improve the bioavailability of therapeutic peptides

et al. 2016

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“…The importance of the type of glycan and glycosidic linkage on the aggregation ability is also confirmed by other studies. The results obtained comparing the tendency to fibril formation of prion‐derived glycopeptides containing either mannose, or galactose or N‐acetylgalactosamine at a specific Ser residue showed that mannosylation and N‐GalNAcylation had the strongest antiamyloidogenic effect, while galactosylation only retarded amyloid formation (Figure ). Semisynthetic full length variants of prion protein carrying monodisperse polyethyleneglycol (PEG), as mimic of N‐glycan, at either or both the natural glycosylation sites were used in assays that demonstrated the effect of the modification on both 3D structure and aggregation propensity, with the PEGylated variant acting as an inhibitor of fibril formation when added to the wild‐type PrP …”

Section: Effect On Aggregation and Assemblymentioning

confidence: 99%

“…The position and type of glycosylation affect amyloid formation of prion‐derived glycopeptides. Reproduced with permission from Lin et al…”

Section: Effect On Aggregation and Assemblymentioning

confidence: 99%

Just a spoonful of sugar: Short glycans affect protein properties and functions

Bello

Rovero

Papini

2019

Journal of Peptide Science

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Glycosylation has a strong impact on the chemical and physical properties of proteins and on their activity. The heterogeneous nature of this modification complicates the elucidation of the role of each glycan, thus slowing down the progress in glycobiology. Nevertheless, the great advances recently made in protein engineering and in the chemical synthesis, and semisynthesis of glycoproteins are giving impulse to the field, fostering important discoveries. In this review, we report on the findings of the last two decades on the importance that the attachment site, linkage, and composition of short glycans have in affecting protein properties and functions.

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Comparison of the anti-amyloidogenic effect of O-mannosylation, O-galactosylation, and O-GalNAc glycosylation

Cited by 14 publications

References 35 publications

Factors affecting the physical stability (aggregation) of peptide therapeutics

Factors affecting the physical stability (aggregation) of peptide therapeutics

Glycosylation, an effective synthetic strategy to improve the bioavailability of therapeutic peptides

Just a spoonful of sugar: Short glycans affect protein properties and functions

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