Bioconjugation in pharmaceutical chemistry.

摘要: Polymer conjugation is of increasing interest in pharmaceutical chemistry for delivering drugs simple structure or complex compounds such peptides, enzymes and oligonucleotides. For long time drugs, mainly with antitumoral activity, have been coupled to natural synthetic polymers the purpose their blood permanence time, taking advantage increased mass that reduces kidney ultrafiltration. However only recently constructs were devised exploit 'enhanced permeability retention' (EPR) effect an efficient tumor targeting, high molecular weight adsorption receptor mediated endocytosis finally a lysosomotropic acid labile bonds cathepsin susceptible polypeptide spacers between polymer drug. New original, very active conjugates this type, as those based on poly(hydroxyacrylate) polymers, are already advanced state development. Labile oligonucleotides, including antisense also successfully view cell penetration stabilization towards nucleases. However, most research activity resides field polypeptides proteins delivery, two following reasons: first all because great number therapeutically interesting now being produced by genetic engineering large quantity and, secondly, these products difficult administer patients several inherent drawbacks. Proteins fact easily digested many endo- exo-peptidases present other body districts; them immunogenic some extent finally, they rapidly excreted Covalent at protein surface was demonstrated reduce eliminate problems, since bound behaves like shield hindering approach proteolytic enzymes, antibodies, antigen processing cell. Furthermore, increase conjugate allows overcome elimination threshold. Many successful results obtained peptides proteins, conjugated water soluble amphiphilic poly(ethylene glycol) (PEG), dextrans, styrenemaleic anhydride. Among asparaginase, interleukin-2 -6 neocarcinostatin, remind antitumor agents, adenosine deaminase employed desease treatment, superoxide dismutase scavenger toxic radicals, hemoglobin oxygen carrier urokinase streptokinase antithrombotic activity. In importance applications without loss catalytic become organic solvents where drug precursors are. The various often chemical problems encountered so different prompted development procedures, characterized specificity mild condition reaction, known 'bioconjugation chemistry'. Bioconjugation developed design new tailor-made wanted weight, shape, functional groups needed coupling positions chain.