Novel Preparation of Decylenediamine-dextran T70 and Inhibitory Activity toward Dihydrofolate Reductase of Decylenediamine-dextran T70-Methotrexate Conjugate(Pharmaceutical)

概要

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The previously reported method for the preparation of decylenediamine-dextran T70 (T70-C_<10>) was improved, and several chemical properties of the polymer support were examined. Methotrexate (MTX) was conjugated to T70-C_<10> by using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride. The T70-C_<10>)-MTX conjugate (T70-C_<10>-MTX) and T70-C_<10> carrying adsorbed MTX (T70-C_<10>-adsorbed MTX) were dialyzed in order to examine the nature of the adsorption of MTX on T70-C_<10>-MTX. Before and after dialysis, the activity of these derivatives was assayed in terms of the binding affinity to dihydrofolate reductase. A more stable T70-C_<10> was obtained by using more severe reaction conditions in the Scruff's base formation between diaminodecane (C_<10>) and oxidized dextran T70 and in the subsequent reduction. Conjugation was successful and the separation by gel-filtration (Sephadex G50) was good. The chemical properties of T70-C_<10> and T70-C_<10>-MTX were consistent and similar to those of the previous preparations. From the dialysis experiment, T70-C_<10>-MTX was estimated to have about 5 to 6% of the inhibitory activity of free MTX.
社団法人日本薬学会の論文
1987-03-25