Glycosaminoglycan conformations and changes on periodate oxidation

Area of Science:

• Biochemistry
• Polymer Chemistry
• Structural Biology

Background:

• Glycosaminoglycans (GAGs) are vital biopolymers with diverse biological roles.
• Understanding GAGs' structural dynamics under chemical modification is crucial for their applications.
• Periodate oxidation is a chemical method to probe GAG structure and conformation.

Purpose of the Study:

• To investigate the effects of progressive periodate oxidation on various GAGs.
• To analyze conformational changes using Circular Dichroism (CD) and High-Performance Liquid Chromatography (HPLC).
• To determine the kinetics and factors influencing GAG oxidation and structural alterations.

Main Methods:

• Progressive periodate oxidation of hyaluronate (HA), chondroitins (CH), dermatan sulfate (DS), and keratan sulfate (KS).
• Monitoring structural changes using Circular Dichroism (CD) spectroscopy.
• Analyzing molecular weight changes via High-Performance Liquid Chromatography (HPLC) with size-exclusion chromatography.
• Calculating oxidation rates using first- and second-order kinetics.

Main Results:

• Periodate oxidation induced significant conformational changes in HA and CH, evidenced by altered CD spectra and decreased molecular weight.
• DS showed minor CD changes and a higher oxidation rate than HA and CH.
• KS remained unaffected by periodate oxidation, indicating resistance to this chemical modification.
• Oxidation kinetics best fit first-order models, with DS oxidizing faster than HA and CH.

Conclusions:

• The extent of periodate oxidation and subsequent property changes depend on the GAG's specific configuration, not solely on oxidation rate.
• Distinct conformational changes between HA and CH are linked to the stereochemistry of their hydroxyl groups.
• CD and HPLC are effective tools for characterizing GAG structural modifications and conformational dynamics.