Proteins are modified by covalently attaching small molecules (coloured or fluorescent reporters, radioactivity) or other macromolecules (enzymes, nucleic acids) to them. Attachment is most often to amine or thiol groups, but other functional groups may also be used. Using bio-orthogonal reactions, labelling of proteins can even be performed inside living organisms. Proteins are modified spontaneously by deamidation, racemisation, oxidation or changes in secondary or tertiary structure, these reactions can limit protein shelf-life.