Solid-Phase O-Glycosylation with a Glucosamine Derivative for the Synthesis of a Glycopeptide

Ryan, Philip; Koh, Andy Hsien Wei; Lohning, Anna; Rudrawar, Santosh

doi:10.1071/ch17201

Cited by 5 publications

(2 citation statements)

References 42 publications

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“…Their highly selective interactions translate to a reduction of side-effects and toxicity. There is a growing interest in peptide science due to an increase in (i) therapeutic targets; (ii) improvements on delivery strategies; (iii) manufacture of large peptide libraries; (iv) synthetic viability and practicality; , and (v) high-throughput screening processes . Though there are drawbacks to peptide-based approaches, notably their lack of physiological stability, these hurdles are progressively being overcome .…”

Section: Peptides Targeting Ad Biomarkersmentioning

confidence: 99%

Peptides, Peptidomimetics, and Carbohydrate–Peptide Conjugates as Amyloidogenic Aggregation Inhibitors for Alzheimer’s Disease

Ryan

Patel

Makwana

et al. 2018

ACS Chem. Neurosci.

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Alzheimer's disease (AD) is a progressive neurodegenerative disorder accounting for 60-80% of dementia cases. For many years, AD causality was attributed to amyloid-β (Aβ) aggregated species. Recently, multiple therapies that target Aβ aggregation have failed in clinical trials, since Aβ aggregation is found in AD and healthy patients. Attention has therefore shifted toward the aggregation of the tau protein as a major driver of AD. Numerous inhibitors of tau-based pathology have recently been developed. Diagnosis of AD has shifted from measuring late stage senile plaques to early stage biomarkers, amyloid-β and tau monomers and oligomeric assemblies. Synthetic peptides and some derivative structures are being explored for use as theranostic tools as they possess the capacity both to bind the biomarkers and to inhibit their pathological self-assembly. Several studies have demonstrated that O-linked glycoside addition can significantly alter amyloid aggregation kinetics. Furthermore, natural O-glycosylation of amyloid-forming proteins, including amyloid precursor protein (APP), tau, and α-synuclein, promotes alternative nonamyloidogenic processing pathways. As such, glycopeptides and related peptidomimetics are being investigated within the AD field. Here we review advancements made in the last 5 years, as well as the arrival of sugar-based derivatives.

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Section: Peptides Targeting Ad Biomarkersmentioning

confidence: 99%

Peptides, Peptidomimetics, and Carbohydrate–Peptide Conjugates as Amyloidogenic Aggregation Inhibitors for Alzheimer’s Disease

Ryan

Patel

Makwana

et al. 2018

ACS Chem. Neurosci.

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“…Targeting upstream cellular processes sometimes yields mechanism-based toxicity, however, and the enzymes governing O-GlcNAc cycling modify thousands of acceptor substrates. We propose that synthetic [3], O-GlcNAc-modified peptidomimetics may qualify as useful chemical tools that probe exclusively the effects of GlcNAc-mediated inhibition of protein self-assembly. Moreover, their strong, reversible binding qualifies peptides as model ex vivo imaging agents.…”

mentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of Bimodal Glycopeptides as Inhibitors of Neurotoxic Protein Aggregation

Ryan

Davey

et al. 2019

The 2nd Molecules Medicinal Chemistry Symposium (MMCS): Facing Novel Challenges in Drug Discovery

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Chemical Synthesis and Biological Applications of O‐GlcNAcylated Peptides and Proteins

2021

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All human cells use O‐GlcNAc protein modifications (O‐linked N‐acetylglucosamine) to rapidly adapt to changing nutrient and stress conditions through signaling, epigenetic, and proteostasis mechanisms. A key challenge for biologists in defining precise roles for specific O‐GlcNAc sites is synthetic access to homogenous isoforms of O‐GlcNAc proteins, a result of the non‐genetically templated, transient, and heterogeneous nature of O‐GlcNAc modifications. Toward a solution, this review details the state of the art of two strategies for O‐GlcNAc protein modification: advances in “bottom‐up” O‐GlcNAc peptide synthesis and direct “top‐down” installation of O‐GlcNAc on full proteins. We also describe key applications of synthetic O‐GlcNAc peptide and protein tools as therapeutics, biophysical structure–function studies, biomarkers, and as disease mechanistic probes to advance translational O‐GlcNAc biology.

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Solid-Phase O-Glycosylation with a Glucosamine Derivative for the Synthesis of a Glycopeptide

Cited by 5 publications

References 42 publications

Peptides, Peptidomimetics, and Carbohydrate–Peptide Conjugates as Amyloidogenic Aggregation Inhibitors for Alzheimer’s Disease

Peptides, Peptidomimetics, and Carbohydrate–Peptide Conjugates as Amyloidogenic Aggregation Inhibitors for Alzheimer’s Disease

Design, Synthesis, and Biological Evaluation of Bimodal Glycopeptides as Inhibitors of Neurotoxic Protein Aggregation

Chemical Synthesis and Biological Applications of O‐GlcNAcylated Peptides and Proteins

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