Selective DNA cleavage by elsamicin A and switch function of its amino sugar group.
We report guanine-specific recognition and selective cleavage of DNA by the antitumor antibiotic elsamicin A equipped with an amino sugar and compare these results with cleavage by chartarin and chartreusin antibiotics. The preferential cutting sites of DNA strand scission with elsamicin A are on the bases adjacent to the 3'-side of guanine residues such as 5'-GN sites, in particular 5'-GG sites. The present results also indicate that (1) the aglycon portion binds intercalatively to the 3'-side of guanine in host DNA, (2) the guanine 2-amino group has an important effect on selective DNA binding of elsamicin A, and (3) the amino sugar residue of elsamicin A facilitates the drug binding into the minor groove of B-DNA. In addition, we found that an acetylation of the amino group on the elsamicin A sugar portion plays an interesting switch function for the activity of elsamicin A. The biological implication of this switch has also been discussed.
Uesugi
M
M
Institute for Chemical Research, Kyoto University, Japan.
Sekida
T
T
Matsuki
S
S
Sugiura
Y
Y
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000494:pharmacology; D000606:Amino Sugars / Q000378:metabolism*; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001345:Autoradiography; D001483:Base Sequence; D001578:Benzopyrans; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004249:DNA Damage; D016172:DNA Fingerprinting; D004214:Distamycins / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D004587:Electrophoresis, Agar Gel; D006027:Glycosides; D007783:Lactones / Q000494:pharmacology; D008969:Molecular Sequence Data; D013050:Spectrometry, Fluorescence
D000348:Aflatoxins; D000606:Amino Sugars; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D001578:Benzopyrans; D004214:Distamycins; D006027:Glycosides; D007783:Lactones; C069756:N-acetylelsamicin A; C069755:chartarin; C030000:stallimycin; D004247:DNA; D016604:Aflatoxin B1; C002185:chartreusin; C049904:elsamicin A