Non-natural amino acids and polypeptides with non-natural amino acids are disclosed. Further, polypeptides with non-natural amino acids that are subject to post-translational modification are disclosed. Additionally, methods of making, purifying, and using non-natural amino acids and polypeptides with non-natural amino acids are disclosed. The non-natural amino acids, by themselves or as part of a polypeptide, can include a wide range of possible functionalities, but typically have at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Uses for the non-natural amino acids and polypeptides with non-natural amino acids include diagnostic, therapeutic, and various biotechnology uses.