title: Novel peptide derivatives of bleomycin A5: synthesis, antitumor activity and interaction with DNA.
abstract: A series of novel amino acid and peptide derivatives of bleomycin (BLM) A(5) were synthesized. All the compounds possessed significant antitumor activities in vitro against HL-60, BGC-823, PC-3MIE8, and MDA-MB-435 cell lines. Their antitumor activities against MDA-MB-435 were 10-fold higher than BLM A5. The DNA cleavage studies indicated that the hydrophobic amino acid or peptide derivatives of BLM A5 could induce higher cleavage ratio of double to single strand DNA than BLM A5. From the DNA binding studies, we found that the derivatives containing either D-conformation amino acid or basic amino acid could facilitate DNA binding of BLM.
authors.affiliation: National Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100083, PR China.
authors.forename: Zhi-Dong
authors.initials: ZD
authors.lastname: Xu
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Su-Long
authors.initials: SL
authors.lastname: Xiao
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001761:Bleomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009691:Nucleic Acid Denaturation; D010455:Peptides / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013696:Temperature
chemical_list: D000970:Antineoplastic Agents; D010455:Peptides; D001761:Bleomycin; C025703:bleomycetin; D004247:DNA