Miles Jonathan R, Wang Xu, de Paz Jose L, Nieto Pedro M
Glycosystems Laboratory, Instituto de Investigaciones Químicas (IIQ), cicCartuja, CSIC and Universidad de Sevilla, C/Américo Vespucio, 49, 41092 Sevilla, Spain.
School of Molecular Sciences, Arizona State University, Tempe, AZ 85281, USA.
Pharmaceuticals (Basel). 2022 Apr 19;15(5):496. doi: 10.3390/ph15050496.
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. Using N-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.
硫酸软骨素E（CS-E）是胚胎中枢神经系统（CNS）中多效生长因子（PTN）的天然配体。已解析出溶液中PTN的一些结构，但尚未报道其结合位点的精确位置。我们使用N标记的PTN和HSQC NMR实验，研究了与对应于最小结合序列的合成CS-E四糖的相互作用。结果与较大糖胺聚糖（GAG）序列的数据一致，并证实了我们的假设，即合成四糖足够长，可以与PTN充分相互作用。我们推测PTN的中心区域是一个内在无序区域（IDR），并且在结合时可能会改变其性质。第二种四糖有两个苄基，对PTN表现出类似的作用。最后，最后测量的化合物聚集，但在此之前，在NMR时间尺度上表现出与缓慢交换相容的行为。我们提出带有和不带有苄基的四糖具有相同的结合位点和模式。
