RESUMO
Chondroitin sulphate forms noncovalent electrostatic biocatalyst-glycosaminoglycan complexes in the solutions of enzymes. Chondroitin sulphate also interacts with enzymes developing complexes after carbodiimide activation of its carboxylic groups. Relatively low-molecular weight of biocatalysts (chymotrypsin, superoxide dismutase) forms stable noncovalent conjugates with the additional interaction as compared with electrostatic complexes. High-molecular weight of enzymes (acid phosphatase) develops covalent conjugates. Chondroitin sulphate is proposed for covalent binding of large proteins and multi-enzymatic complexes to obtain their stabilized derivatives for medical application.
Assuntos
Sulfatos de Condroitina/metabolismo , Condroitina/análogos & derivados , Enzimas/metabolismo , Fosfatase Ácida/metabolismo , Animais , Catálise , Cromatografia em Gel , Quimotripsina/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Cinética , Ratos , Superóxido Dismutase/metabolismoRESUMO
Collagenase was gradually modified by aldehyde dextran and hyaluronidase. The modification increased enzyme stability and widened pH-optimum of its activity against specific and biological substrates. The modified complex with collagenolytic and hyaluronidase activity accumulated in the lungs of mice after intravenous injection. These results demonstrate its possible use for the treatment of lung disorders.
Assuntos
Colagenase Microbiana/farmacologia , Aldeídos/farmacocinética , Aldeídos/farmacologia , Animais , Catálise , Dextranos/farmacocinética , Dextranos/farmacologia , Hialuronoglucosaminidase/farmacocinética , Hialuronoglucosaminidase/farmacologia , Concentração de Íons de Hidrogênio , Masculino , Camundongos , Colagenase Microbiana/farmacocinética , Peso Molecular , Fatores de Tempo , Distribuição TecidualRESUMO
Dextran-modified hyaluronidase was inhaled or intraperitoneally injected for 4 months to mice with silicosis. Stabilized hyaluronidase was shown to have a marked inhibitory effect on the development of lung fibrosis. Drug inhalation proved to be the most effective. An antifibrotic effect of dextran itself has been observed.
Assuntos
Dextranos , Hialuronoglucosaminidase/uso terapêutico , Silicose/tratamento farmacológico , Administração por Inalação , Animais , Avaliação Pré-Clínica de Medicamentos , Estabilidade Enzimática/efeitos dos fármacos , Injeções Intraperitoneais , Pulmão/efeitos dos fármacos , Pulmão/patologia , Ratos , Ratos Endogâmicos , Silicose/patologiaRESUMO
Modified hyaluronidase derivatives have been obtained. Covalent coupling of the enzyme with aldehyde dextran results in 65-85% protein binding to the carrier, residual catalytic activity accounting for 90-100% of the baseline. Modified hyaluronidase is more thermostable than the native enzyme. The data on intravenous drug distribution in the mouse organs are promising and ensure effective use of modified hyaluronidase for the treatment of pulmonary diseases.
