The current invention discloses methods to modify protein and peptide and antigen to treat disease such as pathogen infection, autoimmune diseases and cancer. The method involves increasing the molecular weight of the protein by connecting multiple peptide units with site specific conjugation to extend the in vivo half life. The current invention also discloses methods to construct activatable enzyme, which becomes active when they reach the treatment target, therefore provide higher specificity for treatment. The current invention also relates to methods to treat disease with hemopurification.