Chemoenzymatic synthesis of PSGL-1 glycopeptides: sulfation on tyrosine affects glycosyltransferase-catalyzed synthesis of the O-glycan.
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.
Koeller
K M
KM
Department of Chemistry, The Scripps Research Institute and Skaggs Institute for Chemical Biology, La Jolla, CA, 92037, USA.
Smith
M E
ME
Wong
C H
CH
D000595:Amino Acid Sequence; D002240:Carbohydrate Sequence; D002384:Catalysis; D016695:Glycosyltransferases / Q000378:metabolism*; D013058:Mass Spectrometry; D008562:Membrane Glycoproteins / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D011134:Polysaccharides / Q000138:chemical synthesis*; D013431:Sulfates / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D010455:Peptides; D011134:Polysaccharides; D013431:Sulfates; D014443:Tyrosine; D016695:Glycosyltransferases