Structure-antitumor and hemolytic activity relationships of synthetic peptides derived from cecropin A-magainin 2 and cecropin A-melittin hybrid peptides.
The hybrid peptide (CA-ME) derived from cecropin A(1-8) and melittin (1-12) has potent antibacterial and antimalarial activities. Because the N-terminal sequence 1-12 of magainin 2 is similar to melittin(1-12), CA-MA with CA(1-8) and MA(1-12) and their analogues were designed and synthesized. Antitumor activities of these peptides were evaluated using three small cell lung cancer cell lines. Greater antitumor activity was observed when the residues 16, 18 and 19 of the peptide were hydrophobic (Leu or Val), basic (Lys) and basic (Lys), respectively. The IC50 values of the peptides with the residues were 2 to 4 microM. Residue 12 was related to hemolytic activity rather than antitumor activity. Increase in amphipathicity of P4 enhanced hemolytic activity without significant change in antitumor activity. The alpha-helicity of the peptides in a 30 mM sodium dodecyl sulfate solution was more closely correlated to hemolytic activity than antitumor activity.
Shin
S Y
SY
Peptide Engineering Research Unit, Korea Research Institute of Bioscience and Biotechnology, KIST, Taejon, Korea.
Lee
M K
MK
Kim
K L
KL
Hahm
K S
KS
D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D054806:Magainins; D008555:Melitten / Q000737:chemistry* / Q000494:pharmacology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D029867:Xenopus Proteins
D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D054806:Magainins; D010446:Peptide Fragments; D010455:Peptides; D029867:Xenopus Proteins; C053301:magainin 2 peptide, Xenopus; D008555:Melitten; C031161:cecropin A