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Synthesis, conformation and biology of naphthoxylosides.

Författare

  • Anna Siegbahn
  • Ulrika Aili
  • Agata Ochocinska
  • Martin Olofsson
  • Jerk Rönnols
  • Katrin Mani
  • Göran Widmalm
  • Ulf Ellervik

Summary, in English

Proteoglycans (PG) are polyanionic proteins consisting of a core protein substituted with carbohydrate chains, that is, glycosaminoglycans (GAG). The biosynthesis of GAG can be manipulated by simple xylosides carrying hydrophobic aglycons, which can enter the cell and initiate the biosynthesis. While the importance of the aglycon is well investigated, there is far less information on the effect of modifications in the xylose residue. We have developed a new synthetic protocol, based on acetal protection and selective benzylation, for modification of the three hydroxyl groups in xylose. Thus we have synthesized twelve analogs of 2-naphthyl β-d-xylopyranoside (XylNap), where each hydroxyl group has been epimerized or replaced by methoxy, fluoro, or hydrogen. To gain more information about the properties of xylose, conformational studies were made on some of the analogs. It was found that the (4)C(1) conformation is highly predominant, accompanied by a nonnegligible population of the (2)S(0) conformation. However, deoxygenation at C3 results in a large portion of the (1)C(4) conformation. The GAG priming ability and proliferation activity of the twelve analogs, were investigated using a matched pair of human breast fibroblasts and human breast carcinoma cells. None of the analogs initiated the biosynthesis of GAG, but an inhibitory effect on endogenous PG production was observed for analogs fluorinated or deoxygenated at C4. From our data it seems reasonable that all three hydroxyl groups in XylNap are essential for the priming of GAG chains and for selective toxicity for tumor cells.

Publiceringsår

2011

Språk

Engelska

Sidor

4114-4126

Publikation/Tidskrift/Serie

Bioorganic & Medicinal Chemistry

Volym

19

Dokumenttyp

Artikel i tidskrift

Förlag

Elsevier

Ämne

  • Medicinal Chemistry

Status

Published

Forskningsgrupp

  • Glycobiology

ISBN/ISSN/Övrigt

  • ISSN: 0968-0896