Chondroitin Sulfate Tetrasaccharides: Synthesis, Three-Dimensional Structure and Interaction with Midkine

Chemistry : a European Journal
Cristina SoleraPedro M Nieto

Abstract

The biological activity of midkine, a cytokine implicated in neuro- and tumourigenesis, is regulated by its binding to glycosaminoglycans (GAGs), such as heparin and chondroitin sulfate (CS). To better understand the molecular recognition of GAG sequences by this growth factor, the interactions between synthetic chondroitin sulfate-like tetrasaccharides and midkine were studied by using different techniques. Firstly, a synthetic approach for the preparation of CS-like oligosaccharides in the sequence GalNAc-GlcA was developed. A fluorescence polarisation competition assay was then employed to analyse the relative binding affinities of the synthetic compounds and revealed that midkine interacted with CS-like tetrasaccharides in the micromolar range. The 3D structure of these tetramers was studied in detail by a combination of NMR spectroscopy experiments and molecular dynamics simulations. Saturation transfer difference (STD) NMR spectroscopy experiments indicate that the CS tetrasaccharides bind to midkine in an extended conformation, with similar saturation effects along the entire sugar chain. These results are compatible with docking studies that suggest an interaction of the tetrasaccharide with midkine in a folded structur...Continue Reading

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Citations

Sep 2, 2016·Alcoholism, Clinical and Experimental Research·Amy W Lasek
Jan 20, 2017·Glycoconjugate Journal·L DjerbalJcf Kwok
Jun 18, 2017·Chemistry : a European Journal·Pedro Domínguez-RodríguezJavier Rojo
Mar 19, 2016·Organic & Biomolecular Chemistry·J L de Paz, P M Nieto
Jul 16, 2019·Future Medicinal Chemistry·Shuang YangYinghong Wang
May 27, 2020·SLAS Technology·William P Vignovich, Vitor H Pomin
Jul 31, 2020·Organic & Biomolecular Chemistry·Noelia de la CruzJavier Rojo
Jul 22, 2017·Angewandte Chemie·Jine LiJian Liu
Feb 13, 2019·Beilstein Journal of Organic Chemistry·Teresa Mena-BarragánPedro M Nieto
Apr 25, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Susana MazaPedro M Nieto
Jun 23, 2020·The Journal of Organic Chemistry·Liangzhong ZhangBiao Yu
Apr 3, 2021·Frontiers in Molecular Biosciences·Changkai Bu, Lan Jin
May 29, 2021·Organic & Biomolecular Chemistry·Myriam Torres-RicoPedro M Nieto
Oct 26, 2018·The Journal of Organic Chemistry·Wang YaoZhongjun Li
May 15, 2018·The Journal of Organic Chemistry·Shuang YangPingsheng Lei

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