Neoglycopeptides

V. Wittmann and S. Seeberger, Combinatorial solid-phase synthesis of multivalent cyclic neoglycopeptides, Angew. Chem. Int. Ed., 39 (2000) 4348 -352. 

As illustrated above, peptides have been used as tethering elements for the suitable positioning of carbohydrate moieties. Since the chemistry of glycopeptides is well under control, the approach may appear valuable, at least a priori. This is likely to be true for research investigations. However, as neoglycopeptides should eventually developed into useful therapeutics, the synthesis of novel and metabolically stable neoglycopeptidomitics was undertaken [110-113]. The approach chosen was commensurate to that used for the synthesis of peptoids. 

Convergent Synthesis of Neoglycopeptides by Coupling of 2-Bromoethyl Glycosides to Cysteine (or Homocysteine)... 

Scheme 60 Convergent Synthesis of a Neoglycopeptide by Coupling of a 2-Bromoethyl Glycoside to Cys-teine[4841...

Although the resulting linkages do not precisely replicate natural connections, the simplified procedures allow rapid, convenient access to a wide array of neoglycopeptides that have been shown by some researchers to maintain their native biological activity.20... 

An A -methyl-amino-oxy amino acid has also been incorporated into peptides using standard SPPS procedures. Reaction of these peptides with native reducing sugars yields neoglycopeptides via a chemoselective reaction with the amino-oxy side chains, maintaining the linked sugars in their cyclic conformations and... 

Anomeric thioglycoslydes reacted with tripeptides containing dehydroalanine, derived from selenocysteine by oxidative elimination, thus affording S-linked neoglycopeptides through chemoselective Michael addition (Fig. 28e).116... 

I. Shin, H.-J. Jung, and M.-R. Lee, Chemoselective ligation of maleimidosugars to peptides/ protein for the preparation of neoglycopeptides/neoglycoprotein, Tetrahedron Lett., 42 (2001) 1325-1328. 

Fig. 2.7.6. Structure of multivalent neoglycopeptides used for spatial screening of lectin ligands [15, 17].

---