Kalvin D M, Huang C H, Lischwe M A, Peters E H, Prestayko A W, Crooke S T
Cancer Chemother Pharmacol. 1981;7(1):41-50. doi: 10.1007/BF00258212.
The constituents of the antitumor agent auromomycin have been analyzed to determine their DNA-breakage activities. Spectral analysis showed that the methanol extract contained 70% of the non-peptide chromophore, whereas the residue contained 20%. Amino acid analysis of the methanol extract showed that it contained 21%-26% of the original auromomycin polypeptides. The DNA-degradation activity of the extract was 121% +/- 28% of that of the untreated auromomycin, whereas that of the residue was only 22% +/- 3.8%. Mixing of the residue and the methanol extract resulted in the loss of three-fourths of the total activity. Agarose gel electrophoretic analysis showed that the single-strand DNA breakage activity of the methanol extract was 6.5-fold greater than that of the double-strand DNA-breakage activity. The difference in the total DNA-cleavage activity of the untreated, methanol-treated, and remixed auromomycin preparations may suggest the occurrence of certain non-peptide chromophore-polypeptide interactions in both the untreated and the remixed preparations. This is consistent with the fluorescent changes observed upon mixing of the extract and residue. Fractionation of the methanol extract by Sephadex chromatography revealed that several column fractions which were enriched with non-peptide chromophore relative to the polypeptides contained in them still had significant DNA-degradation activity. These studies suggest that the non-peptide chromophore in the auromomycin preparation may contribute to most of the observed DNA breakage activity.
已对抗肿瘤药物金霉素的成分进行了分析，以确定它们的DNA断裂活性。光谱分析表明，甲醇提取物含有70%的非肽发色团，而残留物含有20%。甲醇提取物的氨基酸分析表明，它含有原始金霉素多肽的21%-26%。提取物的DNA降解活性是未处理金霉素的121%±28%，而残留物的DNA降解活性仅为22%±3.8%。将残留物与甲醇提取物混合导致总活性损失了四分之三。琼脂糖凝胶电泳分析表明，甲醇提取物的单链DNA断裂活性比双链DNA断裂活性高6.5倍。未处理、甲醇处理和重新混合的金霉素制剂在总DNA切割活性上的差异可能表明在未处理和重新混合的制剂中都发生了某些非肽发色团-多肽相互作用。这与提取物和残留物混合时观察到的荧光变化一致。通过葡聚糖凝胶色谱法对甲醇提取物进行分级分离表明，相对于其中所含的多肽，几个富含非肽发色团的柱级分仍具有显著的DNA降解活性。这些研究表明，金霉素制剂中的非肽发色团可能是观察到的大部分DNA断裂活性的原因。
