p2H dependence of the exchange with the solvent of interior amide protons in basic pancreatic trypsin inhibitor modified by reduction of the disulfide bond 1438

This letter is presented to point out that this new result is incompatible with a recently proposed amide proton exchange mechanism (Hilton & Woodward, 1979) which was used to reinterpret the previously reported exchange data obtained with a group of trypsin inhibitor-related proteins.

Abstract

In a chemical modification of the basic pancreatic trypsin inhibitor obtained by reduction of the disulfide bond 1438 and protection of the cysteinyl side-chains by aminoethylation, the rates of exchange of individual interior amide protons with deuterium of the solvent were measured over the p2H range from 0.6 to 9.8 by proton nuclear magnetic resonance. Over this entire p2H range the exchange of the individual amide protons in the modified protein was 100 to 1000 times faster than in the native inhibitor, which correlates with the different thermal stabilities of the two proteins. This letter is presented to point out that this new result is incompatible with a recently proposed amide proton exchange mechanism (Hilton & Woodward, 1979) which was used to reinterpret our previously reported exchange data obtained with a group of trypsin inhibitor-related proteins.