Chemoenzymatic synthesis of PSGL-1 glycopeptides : Sulfation on tyrosine affects glycosyltransferase-catalyzed synthesis of the O-glycan

• Published in: Bioorganic & medicinal chemistry 2000-05, Vol.8 (5), p.1017-1025
• Main Authors: KOELLER, K. M, SMITH, M. E. B, WONG, C.-H
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Bioconversions. Hemisynthesis; Biological and medical sciences; Biotechnology; Carbohydrate Sequence; Catalysis; Fundamental and applied biological sciences. Psychology; Glycosyltransferases - metabolism; Mass Spectrometry; Membrane Glycoproteins - chemical synthesis; Membrane Glycoproteins - chemistry; Membrane Glycoproteins - metabolism; Methods. Procedures. Technologies; Molecular Sequence Data; Nuclear Magnetic Resonance, Biomolecular; Peptides - chemical synthesis; Peptides - chemistry; Peptides - metabolism; Polysaccharides - chemical synthesis; Sulfates - metabolism; Tyrosine - metabolism
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/s0968-0896(00)00041-9

PSGL-1 is the primary glycoprotein ligand for P-selectin during the inflammatory response. Interestingly, the N-terminal sequence, containing both a site of tyrosine sulfation and an O-glycan, has been shown to bind to P-selectin with an affinity similar to full-length PSGL-1. To further characterize this system, the synthesis of glycopeptides from PSGL-1 was undertaken. The synthesis involved both solution- and solid-phase synthesis, as well as enzymatic transformations. During the synthesis, notable reactivity differences of the glycosyltransferases toward sulfated and unsulfated versions of the same glycopeptides were observed.