A synthetic approach to ‘click’ neoglycoprotein analogues of EPO employing one-pot native chemical ligation and CuAAC chemistry

Lee, D. J.; Cameron, Alan J.; Wright, Tom H.; Harris, Paul W. R.; Brimble, Margaret A.

doi:10.1039/c8sc03409e

Cited by 12 publications

(6 citation statements)

References 45 publications

(48 reference statements)

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“…Several groups have reported the synthesis of EPO with homogeneous glycoforms, and the effect of N -glycans on their biological activities has been investigated [ 112 , 115 , 116 , 118 , 119 , 120 ]. In addition, various neoglycoprotein analogues of EPO have been reported [ 121 , 122 , 123 , 124 ]. Kajihara et al synthesized five types of EPO, which is introduced sialic acid containing N -glycans into three N -glycosylation sites with different patterns, and showed the relationship between glycosylation sites and hematopoietic activities [ 115 ].…”

Section: Functional Analysis Of N -Glycans On Gmentioning

confidence: 99%

Recent Advances in the Chemical Biology of N-Glycans

2021

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Asparagine-linked N-glycans on proteins have diverse structures, and their functions vary according to their structures. In recent years, it has become possible to obtain high quantities of N-glycans via isolation and chemical/enzymatic/chemoenzymatic synthesis. This has allowed for progress in the elucidation of N-glycan functions at the molecular level. Interaction analyses with lectins by glycan arrays or nuclear magnetic resonance (NMR) using various N-glycans have revealed the molecular basis for the recognition of complex structures of N-glycans. Preparation of proteins modified with homogeneous N-glycans revealed the influence of N-glycan modifications on protein functions. Furthermore, N-glycans have potential applications in drug development. This review discusses recent advances in the chemical biology of N-glycans.

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Section: Functional Analysis Of N -Glycans On Gmentioning

confidence: 99%

Recent Advances in the Chemical Biology of N-Glycans

2021

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“…Recently, Brimble and co‐workers reported the total chemical synthesis of a 165‐amino acid homogeneous EPO analogue, by employing a one‐pot NCL and copper(I)‐catalysed azide‐alkyne cycloaddition (CuAAC) to afford a “clicked” glycosylated EPO variant (Scheme 7). [33] In this strategy, the peptide sequence was divided into five fragments (EPO 1–29, 30–67, 68–97, 98–127, 128–165). The synthesis of non‐thioester fragment 128–165 was performed using Fmoc‐SPPS strategy under microwave conditions.…”

Section: Chemical‐ and Semisyntheses Of Homogeneous Epo Glycoformsmentioning

confidence: 99%

Recent Progress in the Synthesis of Homogeneous Erythropoietin (EPO) Glycoforms

et al. 2020

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Erythropoietin (EPO) has been regarded as a therapeutic glycoprotein for the clinical treatment of anaemia since its approval by the Food and Drug Administration (FDA) in 1989. Commercial production of the 165‐residue glycoprotein is by recombinant protein expression using mammalian cell lines that renders a complex mixture of glycoforms that have an identical amino acid sequence but variations in the structures of the pendant glycans. This heterogeneous nature of human recombinant EPO restricts structural and bioactivity studies in medicinal chemistry. Consequently, chemical synthesis provides an elegant approach for the preparation of complex homogeneous glycoproteins from a readily accessible pool of amino acids and sugars. In addition, the combination of chemical and biosynthesis enables robust and large‐scale production of homogeneous EPO. The scope of this minireview is to summarise the recent advances in the chemical and semisyntheses of homogeneous EPO glycoforms, highlighting the versatile approaches to the preparation and structural manipulations of the carbohydrate chains incorporated into synthetic EPO glycoproteins.

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“…Alkynes are classified as a new material, pharmaceutical intermediates, nanometer molecular devices as well as the important to build the skeleton in natural product synthesis. 32,33 One of the most commonly used synthetic macromolecular triazole is a method of terminal alkynes and sodium azide as raw material, the Cu (Ⅰ) catalytic Click reaction to finish. 34,35 The method can get high yield of target product, so the alkyne class substrates play a very important role in the middle of the Click reaction.…”

Section: The Effects Of Different Compounds Containing Alkynementioning

confidence: 99%