title: Role of pronase-resistant peptide segments of the antitumor protein antibiotics, auromomycin and macromomycin, in stabilizing cytocidal activity of the chromophore moieties to carcinoma cells.
abstract: The free chromophores isolated from the antitumor protein antibiotics, auromomycin (AUR) and macromomycin (MCR), were rapidly inactivated by incubation in serum-containing medium at 37 degrees C in the dark with respect to cytocidal activity to human lung carcinoma A549 cells. Under the same conditions, the intact antibiotics, their pronase-hydrolysates and reconstituents from the chromophores and apo-proteins were stable. Intact and reconstituted AUR and MCR were more resistant to pronase digestion than the apo-proteins. The analyses of the pronase-hydrolysates of AUR and MCR by SDS-polyacrylamide gel electrophoresis and ultrafiltration showed that the antibiotics (13 kilodaltons (kDa] were degraded to produce peptide fragments (1-3 kDa) in which most cytotoxicity of the pronase-hydrolysates resided. The pronase-hydrolysates exhibited a differential cytocidal activity to normal diploid fibroblasts (WI38), their SV40-transformants (VA13) and carcinoma cells (A549) of human lung origin as was observed for the intact antibiotics. These results indicate that specific interaction between the chromophores and the pronase-resistant peptide segments (1-3 kDa) of the protein moiety stabilizes the cytocidal activity of the chromophores and also protects the peptide segments from pronase digestion.
mesh_terms: D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000187:drug effects* / Q000196:embryology; D008175:Lung Neoplasms / Q000503:physiopathology*; D010455:Peptides / Q000633:toxicity; D011402:Pronase; D013539:Simian virus 40 / Q000235:genetics; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D010455:Peptides; C001666:auromomycin; D011402:Pronase