Chemical Synthesis of Glycoproteins

SCHEME 11.7 Glycopeptide- thioesters by Boc-SPPS conditions. DEPBT, 3-(diethoxyphosphoryloxy)-l,2,3-benzotriazin-4(3//)-one. 

Several syntheses of notable glycoproteins have been reported in the literature, and some examples are briefly described in the sections that follow. The criteria for the following examples were the attainment of a correct fold, bioactivity, and large molecular weight of the target glycoproteins. 

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Chemical Synthesis of Glycoproteins 3.1 Advances in Chemical Ligation... 

For this purpose, Ag zeolite and Ag, developed by Garegg25 and Paulsen,26 respectively, have been widely employed (Scheme 7.6). Reactions using these activators have found practical use in synthetic studies on glycoprotein glycans and glycolipids. For instance, Paulsen reported the chemical synthesis of the core pentasaccharide structure 6 common to all types of Asn-linked glycans, using the Ag... 

Using NCL, Bertozzi et al. first demonstrated the total chemical synthesis of the native antibacterial glycoprotein diptericin consisting of two O-linked GalNAc residues at positions ThrlO and Thr54 of an 82-amino acid chain (Scheme 11.8) [67],... 

Shin, Y, Winans, K A, Backes, B J, Kent, S B. H, EUman, J A, Bertozzi, C R, Fmoc-based synthesis of peptide- thioesters apphcation to the total chemical synthesis of a glycoprotein by native chemical ligation, J. Am. Chem. Soc., 121, 11684-11689, 1999. 

Ogawa and coworkers have also extensively described synthetic studies on glycoprotein oligosaccharides and mannose-containing glycosphingolipids using similar reactions [26,27, 28,29] (O Scheme 9). For instance, the reaction of 14 with disaccharide 15 afforded 16 (o = 1.1 1), which was used as the key intermediate in their first chemical synthesis of a sialic acid-containing complex-type undecasaccharide [30]. 

Chemical synthesis of a glycoprotein via native chemical ligation... 

L. A. Marcaurelle and C. R. Bertozzi, Mini review recent advances in the chemical synthesis of mucin-like glycoproteins, Glycobiology, 12 (2002) 69R-77R. 

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