Hydroxylated oxanes as xyloside analogs for determination of the minimal binding requirements of β4GalT7

Research output: Contribution to journalArticle

Abstract

β-1,4-Galactosyltransferase 7 (β4GalT7) is a key enzyme in the biosynthesis of glycosaminoglycan (GAG) chains. Natural and synthetic xylosides can be used to both inhibit and prime GAG synthesis by acting as inhibitors or substrates for β4GalT7. In this report, we exploit hydroxylated oxanes as deoxygenated xyloside analogs to clarify the minimum protein-ligand interactions required for galactosylation and/or inhibition. Enantiomerically pure substances were synthesized using a chiral pool approach whereas the corresponding racemates were obtained from simple starting materials. The results of a β4GalT7 assay show that a single hydroxyl group on an oxane ring is insufficient to induce galactosylation or inhibition, which implies that at least two substituents, one of which being 3-OH, needs to be present.

Details

Authors
Organisations
External organisations
  • Lund University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medicinal Chemistry

Keywords

  • Chiral pool approach, De novo synthesis, Mechanistic probes, Xyloside analogs, β4GalT7
Original languageEnglish
Pages (from-to)3466-3469
Number of pages4
JournalTetrahedron Letters
Volume58
Issue number35
Publication statusPublished - 2017 Aug 30
Publication categoryResearch
Peer-reviewedYes