Pleiotrophin Interaction with Synthetic Glycosaminoglycan Mimetics

Jonathan R. Miles, Xu Wang, Jose L. de Paz, Pedro M. Nieto

Research output: Contribution to journalArticlepeer-review

Abstract

Chondroitin sulfate (CS) E is the natural ligand for pleiotrophin (PTN) in the central nervous system (CNS) of the embryo. Some structures of PTN in solution have been solved, but no precise location of the binding site has been reported yet. Using15N-labelled PTN and HSQC NMR experiments, we studied the interactions with a synthetic CS-E tetrasaccharide corresponding to the minimum binding sequence. The results agree with the data for larger GAG (glycosaminoglycans) sequences and confirm our hypothesis that a synthetic tetrasaccharide is long enough to fully interact with PTN. We hypothesize that the central region of PTN is an intrinsically disordered region (IDR) and could modify its properties upon binding. The second tetrasaccharide has two benzyl groups and shows similar effects on PTN. Finally, the last measured compound aggregated but beforehand, showed a behavior compatible with a slow exchange in the NMR time scale. We propose the same binding site and mode for the tetrasaccharides with and without benzyl groups.

Original languageEnglish (US)
Article number496
JournalPharmaceuticals
Volume15
Issue number5
DOIs
StatePublished - May 2022

Keywords

  • N-HSQC
  • chondroitin sulphate type E
  • glycosaminoglycan
  • NMR

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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