| C1027 is a new macromolecular antitumor antibiotic produced by Streptomyces globisporus C1027. Its molecule is composed of an enediyne chromophore and an apoprotein through non-covalent bond binding. Molecular weight is 845 dalton for the chromophore and 10500 dalton for the apoprotein respectively. C1027 inhibits mainly DNA synthesis and shows extremely potent cytotoxicity to cultured cancer cells. C1027 is the most potent of the macromolecular peptide antitumor antibiotics ever reported. This study was set to improve the methods for C1027 purification, to develop assays for monitoring C1027 biological activity, to elucidate the relationship between C1027 molecule composition and antitumor activity, and to prepare highly-potent conjugates of monoclonal antibody (McAb) and C1027 by using new methods, and to observe the effect of the conjugates.A new method of hydroxyapatite chromatography has been developed for isolation and purification of C1027. The purified C102 7 was highly active. As determined by clonogenic assay, the IC50 value of C1027 against hepatoma cells was 5.6×10-16M. Compared with the previous method of DEAE-cellulose chromatography, the new method was simpler in procedure, offered higher yields and retained better activity. The quality of C1027 can be controlled by methods of antibacterial assay, spermatogonial assay, clonogenic assay, SDS-PAGE and HPCE assay, etc.C1027 was separated into apoprotein and chromophore parts by methanol extraction. The chromophore possessed highly potent cytotoxicity and IC50 value was 1.8×10-16M. By contrast, the apoprotein had only a weak cytotoxicity to...
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