Medicinal Chemistry

Utilisation of Chromatographic and Electrophoretic Separation Techniques for the Detection of Protein Post-Translational Modifications

Abstract

Wayne Grant Carter

Aberrant post-translational modifications (PTMs) of proteins and the resultant disturbances of cellular signaling pathways typify many disease states. Hence the detection, localisation, and quantitation of PTMs represent important elements of disease analysis. Herein, chromatographic and electrophoretic methodology that may be exploited to first detect the protein(s) that is post-translationally modified, determine the site(s) of the PTM, quantify the stoichiometry of the modification, and then evaluate its stability is discussed. For proteins at which multiple PTMs occur, synthetic peptides that only encompass selected modification site(s) are useful for restricting analysis to specific PTMs. Suggestions for rational peptide design for studying discrete PTMs are detailed. Finally, intrinsic to these analyses of PTMs is the requirement of an evaluation of the functional outcome of the PTM.