Biomedical Engineering Reference
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FIGURE 10.10 Coenzyme B 12 . The prosthetic group in vitamin B 12 . Besides coordinating to four corrin
nitrogen atoms (blue), the cobalt(III) ion is also bound to an axial ligand, nitrogen from a benzimidazole
group (not shown). The vacant sixth position is a binding site for substrates and is indicated with a stick point-
ing upward. A phosphate group (orange) is seen in the lower right corner. The coordinates are taken from the
Protein Data Bank (1CB7).
(A)
(B)
FIGURE 10.11
Platinum anticancer agents. Cisplatin (A). Oxaliplatin (B).
However, the drugs are partly selective toward cancer cells as they are more effective against prolif-
erating cell than resting cells, where no DNA replication may occur over long periods of time.
Despite extensive research, only three platinum drugs have succeeded in reaching the market
in the Western World while a fourth (satraplatin) is expected to be released in 2008. The relevant
drugs are shortly introduced in the following text. For details concerning platinum interactions with
proteins, biochemical pathways, and cancer type specii c activities we refer to Chapter 23.
Cisplatin ( cis -diamminedichloroplatinum(II); cis -DDP; Figure 10.11A), the i rst platinum
anticancer agent to be used clinically, was discovered serendipitously in 1970 as an inhibitor of E. coli
cell division. The two ammine ligands represent nonleaving groups and the chloride ions constitute
exchangeable groups, which can be replaced by other ligands (nucleophiles). The second and third
generation analogues to cis -DDP have been developed by simple substitution of the ammine ligands
or chloride leaving groups of cisplatin. In “carboplatin” [ cis -diammine-1,1-cyclobutanedicarboxyl-
atoplatinum(II)], the two chloride ions have been substituted with less labile carboxylato groups.
Carboplatin shows less toxic side effects than cisplatin and has now replaced the latter in many
clinical situations.
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