Synthesis of a new inhibitor of the UDP-GalNAc:polypeptide galactosaminyl transferase.
Reaction of UDP-glucose with 1-hexadecanesulfonyl chloride (C16H33SO2Cl) in pyridine gave a new inhibitor of O-glycosylation. This reaction product was purified by TLC and shown by 1H-NMR and by chemical analysis of phosphorus to be uridine 5'-phosphoric (1-hexadecanesulfonic) anhydride. This compound was tested against the GalNAc transferase. The UMP-hexadecanesulfonic-anhydride did inhibit this enzyme with 50% inhibition requiring 160 microM. The inhibition with respect to UDP-GalNAc concentration was of the competitive type. We also synthesized the UMP-1-octanesulfonic anhydride (C8) and the UMP-butanesulfonic anhydride (C4) to see way effect fatty acid had on activity. The inhibition was in the order C16:C8:C4.
Hatanaka
K
K
Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284.
Slama
J T
JT
Elbein
A D
AD
D000812:Anhydrides / Q000737:chemistry; D005700:Galactosyltransferases / Q000037:antagonists & inhibitors*; D006023:Glycoproteins / Q000096:biosynthesis; D006031:Glycosylation; D009682:Magnetic Resonance Spectroscopy; D008345:Manganese / Q000494:pharmacology; D017350:N-Acetylgalactosaminyltransferases; D013329:Structure-Activity Relationship; D014536:Uridine Diphosphate N-Acetylgalactosamine / Q000737:chemistry; D014542:Uridine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000097763:Polypeptide N-acetylgalactosaminyltransferase
D000812:Anhydrides; D005700:Galactosyltransferases; D006023:Glycoproteins; D008345:Manganese; D017350:N-Acetylgalactosaminyltransferases; D014536:Uridine Diphosphate N-Acetylgalactosamine; D014542:Uridine Monophosphate; D000097763:Polypeptide N-acetylgalactosaminyltransferase; C068470:uridine 5'-phosphoric (1-hexadecanesulfonic)anhydride