Abstract:
:N1999A2 (NA2) is a new non-protein antitumor antibiotic that contains a stable 9-membered ring enediyne chromophore similar to a neocarzinostatin chromophore (NCS-chr). We have compared DNA cleavage reactions between NA2 and NCS-chr, and also clarified some characteristics of DNA strand scission by NA2. It was found that: (1) NA2 is considerably stable in nature, (2) the compound intercalates into base pairs of a DNA minor groove and decreases its base-attacking frequency in the order of T>A> C>G, (3) the base-sequence specificity 5(')-GGT/3(')-CCA presented by NA2 is significantly related to recognition of the base pair with the naphthoate moiety, and (4) the different cleavage property between NCS-chr and NA2 is associated with the presence or absence of an aminoglycoside residue. Based on the results of the site-specific cleavage by NA2 for certain bulged DNAs and a fluorescence study of NA2-DNA oligomer complexes, the DNA interaction mode of NA2 has also been examined. These results provide important information to design a new enediyne molecule for a DNA target.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Miyagawa N,Sasaki D,Matsuoka M,Imanishi M,Ando T,Sugiura Ydoi
10.1016/s0006-291x(03)00925-2subject
Has Abstractpub_date
2003-06-20 00:00:00pages
87-92issue
1eissn
0006-291Xissn
1090-2104pii
S0006291X03009252journal_volume
306pub_type
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