Factors Affecting Hydrogen-Deuterium Exchange of Biological Molecules

Factors Affecting Hydrogen-Deuterium Exchange of Biological Molecules 

When exchange studies of insulin were first published (Hvidt and Linderstrom-Lang, 1954), it was suggested that the peptide hydrogens which did not exchange with 

Exchange studies with di- and tripeptides (Nielsen et ai, 1960) gave results similar to those obtained in the case of JV-methylacetamide. The rates varied with pD, indicative of acid and base catalysis, and the minimum rates ( 0.6min for glycylglycine and 0.3 min for the JV-terminal peptide group of alanylglycyl- 

The polypeptide, poly-DL-alanine, also gave exchange results (Bryan and Nielsen, 1960) similar to those obtained for the smaller peptides. The exchange reaction followed first-order kinetics, the rate constants (0.14 to 1.2 min ) were of the same order of magnitude as for the simpler peptides and the exchange was subject to and OH (D and OD ) catalysis. The pH (pD) dependence of the exchange rate has been summarized in two approximate equations (Bryan and Nielsen, 1960) 

Leichtling and Klotz (1966) extended such studies to other model compounds and examined the three features characteristic of exchange reactions, namely, pD , and Ed, the activation energy of the exchange reaction. They derived mathematical expressions relating these features to the factors under consideration and analyzed the experimental data in terms of these expressions. The rate constant for the D and OD catalyzed exchange reaction can be expressed as Eq. (9) 

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