Increased toxicity and DNA cross-linking by peptide bound m-L-sarcolysin (Peptichemio) as compared to melphalan and m-L-sarcolysin in human melanoma cell lines.
Alteration of the melphalan molecule by shifting the di(2-choroethyl)aminogroup from the para- to the meta-position of the phenylalanine residue results in m-L-sarcolysin. By covalent conjugation of different amino acids at the amino- and carboxylgroups of this molecule, a mixture of six peptides known as Peptichemio has been synthesized. In a previous investigation we found that Peptichemio was less toxic to human lymphoblasts than m-L-sarcolysin. In contrast, in the present investigation we found that Peptichemio has higher cytotoxic effect than m-L-sarcolysin on two human melanoma cell lines. The higher cytotoxicity was paralleled by a higher induction of DNA cross-links by Peptichemio as compared to m-L-sarcolysin. A comparative analysis of the six peptides on Peptichemio showed differences in cytotoxic effects on a melanoma cell line. One of the six peptides displayed a considerably higher cytotoxicity than peptichemio itself.
Lewensohn
R
R
Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
Ehrsson
H
H
Hansson
J
J
Ringborg
U
U
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000187:drug effects*; D004347:Drug Interactions; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008545:Melanoma; D008558:Melphalan / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010440:Peptichemio / Q000494:pharmacology*
D003432:Cross-Linking Reagents; D004273:DNA, Neoplasm; C053596:metamelfalan; D010440:Peptichemio; D008558:Melphalan