New insights into sequence recognition process of esperamicin A1 and calicheamicin gamma 1I.: origin of their selectivities and "induced fit" mechanism.
This study addresses the DNA sequence recognition event of the enediyne antibiotics esperamicin A1 and calicheamicin gamma 1I by the use of synthetic DNA oligomers, salt effects, and circular dichroism studies. The results reported here provide several important insights: (1) esperamicin A1 requires a purine/pyrimidine trimer in host DNA for favorable interaction, (2) the sequence selectivity of esperamicin C is an origin of esperamicin A1 and calicheamicin gamma 1I selectivities, (3) in the target recognition by esperamicin C, its total structure and hydrophobicity are important, and (4) the binding of hydrophobic esperamicin to DNA duplex induces dehydration and conformational change of the host DNA. The specific sequence recognition process of esperamicin/calicheamicin has been discussed.
Uesugi
M
M
Institute for Chemical Research, Kyoto University, Japan.
Sugiura
Y
Y
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D053281:Enediynes; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D053281:Enediynes; C055955:calicheamicin gamma(1)I; D004247:DNA; C047543:esperamicin A1