Glycosystems Laboratory, Instituto de Investigaciones Químicas (IIQ), cicCartuja, CSIC and Universidad de Sevilla, Americo Vespucio, 49, 41092 Sevilla, Spain.
Int J Mol Sci. 2022 Mar 11;23(6):3026. doi: 10.3390/ijms23063026.
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.
多效蛋白（PTN）是一种神经营养因子，通过与硫酸化糖胺聚糖（GAGs）相互作用参与胚胎中枢神经系统（CNS）的发育和神经干细胞的调节。软骨素硫酸盐（CS）是 CNS 中的天然配体。我们之前曾使用配体观察 NMR 技术研究了这里使用的四糖与 MK（中期因子）之间的复合物。本工作描述了使用相同的 NMR 瞬变技术，CS 型和类似物的合成模型四糖文库与 PTN 之间的相互作用。我们得出的结论是：（1）结合后配体的整体结构不变，（2）在配体结构中引入亲脂性取代基可提高结合强度，（3）结合强度低于 MK，（4）STD-NMR 结果与多种结合模式兼容，（5）用 IdoA 替代 GlcA 与结合无关。因此，我们可以得出结论，CS 衍生物与 PTN 和 MK 的结合相似，并且与相同基本构象的多种结合模式兼容。
