The Interaction between Chondroitin Sulfate and Dermatan Sulfate Tetrasaccharides and Pleiotrophin.

María Jose García-Jiménez,Myriam Torres-Rico,Pedro M Nieto,José L De Paz

doi:10.3390/ijms23063026

Abstract

Pleiotrophin (PTN) is a neurotrophic factor that participates in the development of the embryonic central nervous system (CNS) and neural stem cell regulation by means of an interaction with sulfated glycosaminoglycans (GAGs). Chondroitin sulfate (CS) is the natural ligand in the CNS. We have previously studied the complexes between the tetrasaccharides used here and MK (Midkine) by ligand-observed NMR techniques. The present work describes the interactions between a tetrasaccharide library of synthetic models of CS-types and mimetics thereof with PTN using the same NMR transient techniques. We have concluded that: (1) global ligand structures do not change upon binding, (2) the introduction of lipophilic substituents in the structure of the ligand improves the strength of binding, (3) binding is weaker than for MK, (4) STD-NMR results are compatible with multiple binding modes, and (5) the replacement of GlcA for IdoA is not relevant for binding. Then we can conclude that the binding of CS derivatives to PTN and MK are similar and compatible with multiple binding modes of the same basic conformation.

Highlights

Pleiotrophin (PTN or HB-GAM) is a potent mitogenic cytokine [1] and, together with midkine (MK), constitutes the family of the neurite growth-promoting factors (NEGF)primarily involved in early neural growth and other physiological actions related to mitogenesis or inflammation [2]
They interact with extracellular glycosaminoglycans (GAG) that are fundamental for their activity through interactions with specific membrane receptors
NOE is compatible with the same 3D structure free37/0.7 and bound: 3. Discussion an extended chain, with syn-Φ glycosidic linkages that lead to a helicoidal, quasi-linear shape

Summary

Introduction

Primarily involved in early neural growth and other physiological actions related to mitogenesis or inflammation [2]. They interact with extracellular glycosaminoglycans (GAG) that are fundamental for their activity through interactions with specific membrane receptors. This has been associated with, apart from neural regeneration, other biological events, including tissue repair, cancer metastasis, inflammation, bone development, or Alzheimer’s disease. Phosphatase (RPTP) β/ζ [3], syndecan-3, and anaplastic lymphoma kinase (ALK) [4]. The central region consists of an intrinsically disordered region (IDR). It has two lysine-rich clusters at the N- and

Methods

Results

Conclusion