Publication details
Conformation, recognition by high mobility group domain proteins, and nucleotide excision repair of DNA intrastrand cross-links of novel antitumor trinuclear platinum complex BBR3464
| Authors | |
|---|---|
| Year of publication | 2001 |
| Type | Article in Periodical |
| Magazine / Source | Journal of Biological Chemistry |
| MU Faculty or unit | |
| Citation | |
| Field | Biophysics |
| Keywords | DNA; anticancer drug; platinum; conformation; recognition |
| Description | The new antitumor trinuclear platinum compound [{trans-PtCl(NH3)2}2m- trans-Pt(NH3)2{H2N(CH2)6NH2}2]4+ (designated as BBR3464) is currently in Phase II clinical trials. DNA is generally considered the major pharmacological target of platinum drugs. The bifunctional DNA binding of BBR3464 is characterized by the rapid formation of long-range intra- and interstrand cross-links. We examined how the structures of the various types of the intrastrand cross-links of BBR3464 affect conformational properties of DNA, how these adducts are recognized by HMG1 protein and removed from DNA during in vitro nucleotide excision repair reactions. The results have revealed that intrastrand cross-links of BBR3464 create a local conformational distortion, but none of these cross-links results in a stable curvature. In addition, we have observed no recognition of these cross-links by HMG1 proteins, but we have observed effective removal of these adducts from DNA by nucleotide excision repair. |