The Interaction between Chondroitin Sulfate and Dermatan Sulfate Tetrasaccharides and Pleiotrophin
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 previo...
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| Format: | Article |
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MDPI AG
2022-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/6/3026 |
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| author | María Jose García-Jiménez Myriam Torres-Rico José L. de Paz Pedro M. Nieto |
| author_facet | María Jose García-Jiménez Myriam Torres-Rico José L. de Paz Pedro M. Nieto |
| author_sort | María Jose García-Jiménez |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T19:43:06Z |
| format | Article |
| id | doaj.art-1b7e90c2408b4d3fb09f956f1e5a68a8 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T19:43:06Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1b7e90c2408b4d3fb09f956f1e5a68a82023-11-24T01:30:52ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-03-01236302610.3390/ijms23063026The Interaction between Chondroitin Sulfate and Dermatan Sulfate Tetrasaccharides and PleiotrophinMaría Jose García-Jiménez0Myriam Torres-Rico1José L. de Paz2Pedro M. Nieto3Glycosystems Laboratory, Instituto de Investigaciones Químicas (IIQ), cicCartuja, CSIC and Universidad de Sevilla, Americo Vespucio, 49, 41092 Sevilla, SpainGlycosystems Laboratory, Instituto de Investigaciones Químicas (IIQ), cicCartuja, CSIC and Universidad de Sevilla, Americo Vespucio, 49, 41092 Sevilla, SpainGlycosystems Laboratory, Instituto de Investigaciones Químicas (IIQ), cicCartuja, CSIC and Universidad de Sevilla, Americo Vespucio, 49, 41092 Sevilla, SpainGlycosystems Laboratory, Instituto de Investigaciones Químicas (IIQ), cicCartuja, CSIC and Universidad de Sevilla, Americo Vespucio, 49, 41092 Sevilla, SpainPleiotrophin (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.https://www.mdpi.com/1422-0067/23/6/3026carbohydrate–protein interactionpleiotrophinchondroitin sulfateGAG synthesistransient NMR methodsSTD-NMR spectroscopy |
| spellingShingle | María Jose García-Jiménez Myriam Torres-Rico José L. de Paz Pedro M. Nieto The Interaction between Chondroitin Sulfate and Dermatan Sulfate Tetrasaccharides and Pleiotrophin International Journal of Molecular Sciences carbohydrate–protein interaction pleiotrophin chondroitin sulfate GAG synthesis transient NMR methods STD-NMR spectroscopy |
| title | The Interaction between Chondroitin Sulfate and Dermatan Sulfate Tetrasaccharides and Pleiotrophin |
| title_full | The Interaction between Chondroitin Sulfate and Dermatan Sulfate Tetrasaccharides and Pleiotrophin |
| title_fullStr | The Interaction between Chondroitin Sulfate and Dermatan Sulfate Tetrasaccharides and Pleiotrophin |
| title_full_unstemmed | The Interaction between Chondroitin Sulfate and Dermatan Sulfate Tetrasaccharides and Pleiotrophin |
| title_short | The Interaction between Chondroitin Sulfate and Dermatan Sulfate Tetrasaccharides and Pleiotrophin |
| title_sort | interaction between chondroitin sulfate and dermatan sulfate tetrasaccharides and pleiotrophin |
| topic | carbohydrate–protein interaction pleiotrophin chondroitin sulfate GAG synthesis transient NMR methods STD-NMR spectroscopy |
| url | https://www.mdpi.com/1422-0067/23/6/3026 |
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