Chemical Synthesis of an Erythropoietin Glycoform Containing a Complex-type Disialyloligosaccharide

Department of Chemistry, Graduate School of Science, Osaka University, 1-1, Machikaneyama, Toyonaka, 560-0043 Japan.
Angewandte Chemie International Edition (Impact Factor: 11.26). 04/2012; 51(15):3567-72. DOI: 10.1002/anie.201109034
Source: PubMed

ABSTRACT New and improved: New reaction conditions for tert-Boc-based solid-phase peptide synthesis make acid-labile sialyloligosaccharyl peptide α-thioesters accessible. To demonstrate this, a sialyloligosaccharyl-erythropoietin glycoform with 166 amino acid residues was synthesized.

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    • "This development has provided the flexibility to retrosynthetically disconnect the glycoprotein sequence at appropriate junctions and significantly expanded the scope of NCL for protein and glycoprotein synthesis (Payne and Wong, 2010; Unverzagt and Kajihara, 2013). The recent success in the chemical synthesis of glycoprotein hormone a and b subunits (Aussedat et al., 2012; Nagorny et al., 2012), glycosylated human interferon-b (Sakamoto et al., 2012), and full-size erythropoietin (Murakami et al., 2012; Wang et al., 2012) showcases the power of the ligation methods for total glycoprotein synthesis. Moreover, expressed protein ligation (EPL) has been successfully explored for glycoprotein synthesis, in which a large intact protein thioester or an N-terminal Cys-containing protein domain is recombinantly expressed and used as ligation partners (Muir, 2003; Muir et al., 1998; Payne and Wong, 2010; Schwarzer and Cole, 2005). "
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