Experimental strategies to study protein post-translational modification. Enrichment of lysine acetylated (▲), phosphorylated () and glycosylated peptides (■) using different affinity media is shown as examples. A typical workflow for PTM analysis involves extraction of proteins from cells or tissues followed by proteolysis of extracted proteins into peptides, reduction of sample complexity by fractionation (if required), enrichment of PTM peptides by using appropriate methods, LC-MS/(MS) and database searches for identification, quantification and PTM site matching. Different methods can be selected for protein extraction, fractionation, and enrichment of PTM peptides depending on sample type, complexity and targeted analysis.