Analytical techniques used to study the degradation of proteins and peptides: chemical instability

Instability of peptides and proteins can be divided into two forms: chemica l and physical instability. Chemical instability is due to modification/alt eration of amino acid residues. There are several types of degradation reac tions responsible for this instability. Most frequently described reactions are oxidation, reduction, deamidation, hydrolysis, arginine conversion, be ta-elimination and racemisation. However, any study of the degradation of a chemical substance lacks reliability when the analytical methodology, that is used is not properly validated. Especially in the investigation, where degradation processes lead to their parent compounds, validation of the ana lysis is pivotal for the correct interpretation of the results. It is there fore appropriate and useful to assemble an overview of degradation processe s in relation to the analytical methods to monitor them. An overview like t his can help investigators to make the right choices in their analytical ap proach of stability problems. The degradation reactions involved in peptide /protein degradation as well as the methods to monitor them are summarized and discussed. (C) 1998 Published by Elsevier Science B.V. All rights reser ved.