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Sunday 26 March 2006

Definition: Alkylation is the replacement of hydrogen on an atom by an alkyl group. The alkylation of nucleic acids involves a substitution reaction in which a nucleophilic atom (nu) of the nucleic acid displaces a leaving group from the alkylating agent: nu-H + alkyl-Y alkyl-nu + H+ + Y-.

In alkylation chemistry, chlorine is a good leaving group that facilitates nucleophilic attack of nitrogen to form an imminium ion (R3N) in a strained ring system. This readily undergoes alkylation at N7 of guanine to form a monoalkylation adduct.

This process can then be repeated to form the crosslinked DNA. Crosslinking can occur either between two complementary strands of DNA (interstrand), as generated by chlorambucil and melphalan, or within a strand of DNA (intrastrand), as generated by cisplatin.

See also

- alkylating agents