elsamicin-a and stallimycin

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.

Topics: Aflatoxin B1; Aflatoxins; Amino Sugars; Aminoglycosides; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Autoradiography; Base Sequence; Benzopyrans; Distamycins; DNA; DNA Damage; DNA Fingerprinting; Electron Spin Resonance Spectroscopy; Electrophoresis, Agar Gel; Glycosides; Lactones; Molecular Sequence Data; Spectrometry, Fluorescence