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The adhesives industry is increasingly interested in products coming from natural and renewable resources. The aim of the present work was to improve the water resistance of soy-based proteins by using synthetic and formaldehyde-free additives. These include polyamide-amine epichlorohydrin (PAE), different types of isocyanates, and combinations of these cross-linkers between them and with other agents, including metal ions. In addition, the effect of both curing temperature and maturation time was assessed. Performances were evaluated by means of shear strength tests, solubility tests, and spectroscopic analysis. The obtained results showed that while isocyanates reacted completely but with water instead of proteins, tests with PAE were generally successful. In fact, the insoluble residue as well as the shear strength in wet conditions dramatically increased after PAE addition. Moreover, the wet performances of protein/PAE formulations appreciably increased gluing at 60 °C instead of room temperature. Furthermore, the maturation time had a positive effect on the formulations where metal ions were added, both for solubility and wet shear strength. Actually, for the very long conditioning time of 3 months, a significant and substantial increase of wet shear strength was observed for the series protein/PAE/aluminum. [ABSTRACT FROM AUTHOR]