ISSN:
1432-1327
Schlagwort(e):
Key words Molecular diversity
;
HMG-domain proteins
;
Platinum-amino acid complexes
;
Platinum anticancer drugs
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Biologie
,
Chemie und Pharmazie
Notizen:
Abstract We report a new, mechanism-based approach to the screening of pools of potential platinum antitumor drugs. A platinum complex of L-lysine, [Pt(Lys)Cl2] or Kplatin, was selected from mixtures of platinum-amino acid compounds based on the ability of its DNA adducts to bind HMG1 in a gel mobility shift assay. Kplatin, unlike most other platinum antitumor drug candidates, is an (N,O)-chelated complex which binds DNA forming two isomeric 1,2-d(GpG) intrastrand DNA cross-links. Kplatin-modified DNA is specifically recognized by HMG1, HMG1 domain B, and testis-specific HMG, all of which bind to the major cisplatin-DNA adducts. Kplatin is toxic towards the human tumor cell lines HeLa and KM12 with LC50 values of 59.2±7.8 μM and 74 μM, respectively.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/s007750050209
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