Phosphorylated glycopeptides

Rio, S, Beau, J-M, Jacquinet, J-C, Synthesis of sulfated and phosphorylated glycopeptides from the carbohydrate-protein linkage region of proteoglycans, Carbohydr. Res., 255, 103-124, 1994. 

Figure 14.7 Models of phosphorylated high-mannose M7 and a glycopeptide mimic obtained by MD calculation showing similar conformations. They are seen from the point of interaction with the mannose-6-phosphate receptor. Disaccharide phosphates are emphasized as spheres.76...

Systematic investigations of mannose-binding proteins with clustered mannosides other than natural multiantennary oligosaccharides have been rather scarce until recently. However, using 6 -0-phosphorylated mannose disaccharide scaffolded on peptide templates using combinatorial glycopeptide libraries. 

Figure 8. Radioactivity scan of a paper electrophoretogram of NaB[3H7 s reduced hydrolysate of inhibitor glycopeptides (top) and glycopeptides from fi-galactosidase (bottom). Phosphorylated compounds could not be detected in peaks A and B or in the mannitol-6-phosphate region, C. (see the text for details).

H. Franzyk, M. K. Christensen, M. Jorgensen, M. Meldal, H. Cordes, S. Mouritsen, K. Bock. Constrained glycopeptide ligands for MPRs. Limitations of unprotected phosphorylated building blocks. Bioorg. Med. Chem. 1997,5.21-40. 

Let us turn to answering the second question first. Potential precursors of dehydroalanine, by way of -elimination, are the amino acids with functional groups at the /3-carbon atom. Such -elimination reactions are likely to be enzyme-catalyzed in nature. Additionally, the substrates may be suitably substituted at functions, such as the sulfhydryl group (thioether and sulfonium salt formation) or the hydroxyl group (carbohydrate attachment—glycopeptides and proteins phosphorylation). 

The versatility of the side-chain anchoring approach in the synthesis of head-to-tail cyclic peptides is shown by a synthesis of cyclic phos-phorylated glycopeptides. In order to obtain a constrained peptidic inhibitor of mannose 6-phosphate receptor (MPR), Franzyk et al. [40] synthesized three cyclic hexapeptides a-glycosylated with two phosphorylated o (l->2)-... 

The resonance signals (B-D) at 104.9, 103.3 and 100.9 ppm represent those from the anomeric carbon of three species of pyranosides. The signals at 104.9 and 103.3 coincide with the nonreducing terminal mannopyranosyl and internal a(1 2)-D-manno-pyranosyl residues, respectively. The signal at 100.9 ppm has not been identified, but it is known to be eliminated upon removal of the phosphorus at pH 3.5. However, the chemical shift of the anomeric carbon atom of an a-D-mannopyranosyl-l-phosphoryl residue should be around 97.1 ppm (40) which seems to eliminate an a-D-mannopyranosyl-l-phosphoryl group as being attached to the mannan backbone as occurs in the glycopeptide from werneckii... 

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