Unveiling heparin and heparan sulfate conformations : A Journey into paramagnetic NMR analysis.
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Date
2024-03-26Author
Jaime Rodríguez, Juan Carlos
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Heparin (HP) and Heparan sulfates (HS) are vital sulfated polysaccharides found in the extracellular environment., impacting diverse biological functions including cell growth, adhesion, virus recognition, and cancer metastasis. Numerous HP/HS-protein interactions have been elucidated via affinity-based techniques and X-ray crystallography, alongside NMR analysis of their conformations in solution. However, interpreting their conformational dynarnics remains challenging, especially for long saccharides. This study proposes the use of paramagnetic NMR, particularly pseudo-contact shifts (PCS), to understand their conformations and interactions. A synthetic approach linking a glucosamine model to the pararnagnetic probe TAHA was developed, enabling investigation of glycoconjugate complex.ation with lanthanides via NMR. PCS measurements facilitated determination of main confonnations in solution and paramagnetic aoisotropy propenies. Translating knowledge from a GlcNAc model to an HS octasaccharide revealed insights ínto the differences between natural and benzylated 1-1S at a conforma11onal leve!. These findings broaden the application of paramagnetic NMR to chemically synthesized HS molecules, facilitating further analysis of their interactíons with proteins.