Autoactivation of pancreatic trypsinogen is controlled by carbohydrate-specific interaction

•Bovine trypsinogen was found to bind to α-GalNAc, α-Man, and α-Gal.•Activation of trypsinogen by trypsin was specifically inhibited by d-GalN or GalNAc.•The binding of GalNAc to trypsinogen but not to trypsin suppressed autoactivation. Activation of bovine pancreatic trypsinogen (BPTG) by trypsin (BPT) was found to be inhibited by d GalN/GalNAc at pH 5.5, the pH of secretory granules in the pancreas. Binding studies with biotinylated sugar-polymers indicated that BPTG and BPT bind to α-GalNAc, α-Man, and α-Gal better at pH 5.5 than at pH 7.5. Ultraviolet-difference spectra indicated that BPTG binding to α-GalNAc differs substantially from BPTG binding to other sugars. The N-α-benzoyl-d,l-arginine-p-nitroanilide hydrochloride-hydrolyzing activity of BPT was only slightly affected by these sugars. The results indicate that the binding of GalNAc – containing glycoconjugates protects BPTG from autoactivation, and this may be a self-defense mechanism against intrapancreatic activation.