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

Chembiochem : a European Journal of Chemical Biology
Yuxin WangPaul W R Harris

Abstract

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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Citations

Feb 7, 2021·Advanced Drug Delivery Reviews·Raoul Walther, Alexander N Zelikin
Mar 22, 2021·The Journal of Biological Chemistry·James H Prestegard

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