| Autor: |
Esswein A; Department of Molecular and Experimental Medicine, Research Institute of Scripps Clinic, La Jolla, CA 92037., Hänseler E, Montejano Y, Vitols KS, Huennekens FM |
| Jazyk: |
angličtina |
| Zdroj: |
Advances in enzyme regulation [Adv Enzyme Regul] 1991; Vol. 31, pp. 3-12. |
| DOI: |
10.1016/0065-2571(91)90005-7 |
| Abstrakt: |
Carboxypeptidase-A and a monoclonal antibody (KS1/4) directed against a human lung carcinoma cell line (UCLA-P3) were derivatized by treatment with succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate and N-succinimidyl 3-(2-pyridyldithio)propionate, respectively. Admixture of these entities produced a stable conjugate containing 4 to 5 enzyme molecules per molecule of antibody. The conjugate (Mr approximately equal to 300 kDa) was purified to homogeneity by HPLC gel filtration and HPLC ion-exchange chromatography. Neither the catalytic activity of the enzyme nor the antigen-binding capacity of the monoclonal antibody was impaired in the conjugate. UCLA-P3 cells that had been exposed to the conjugate and then washed thoroughly were extremely sensitive to methotrexate alpha-alanine (MTX-Ala), a prodrug form of MTX. At 10(-5) M, MTX-Ala was almost as effective as free MTX in blocking the replication of conjugate-treated cells. These results demonstrate the chemotherapeutic potential of enzyme-monoclonal antibody conjugates used in conjunction with prodrugs. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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