Synthesis of N-alanyl-hyaluronamide with high degree of substitution for enhanced resistance to hyaluronidase-mediated digestion

► N-alanyl-hyaluronamide derivatives were prepared using different amidation methods. ► Three methods were performed in aqueous, mixed and anhydrous solvents. ► The method in anhydrous solvent led to a degree of substitution of 100%. ► N-alanyl-hyaluronamides present enhanced resistance towards enzymatic digestion.