A method of modification of a protein or polypeptide in the presence of a modifying composition capable of providing at least one modification wherein a liquid phase comprising the protein or polypeptide is brought into contact with a solid phase capable of immobilizing the protein or polypeptide and the solid phase carrying the immobilized protein is brought at least once into contact with a liquid phase comprising the composition capable of modifying the protein or polypeptide and modification reaction(s) are allowed to occur. The liquid phase comprising the protein or polypeptide may be a liquid extract of eukaryote or prokaryote cells. The modification may be a acylation, phosphorylation, dephosphorylation, SUMOylation, ubiquitinylation, carboxymethylation, formylation, acetylation, deacetylation, gamma carboxyglutamic acid, norleucine, amidation, deamidation, carboxylation, carboxyamylation, sulfation, methylation, demethylation, hydroxylation, ADP-ribosylation, maturation, adenylation, O-linked glycosylation, N-linked glycosylation, methonine oxidation, and addition of lipid (prenylation).