Elucidating the Targets of Antileukemic Agents: Molecular Mechanisms of Mercaptopurine Action.

Autor:	Krynetskaia, N. F., Krynetski, E. Y.
Předmět:	LEPROSTATIC agents MOLECULAR structure PENICILLAMINE ANTINEOPLASTIC antibiotics METHYLTRANSFERASES DNA
Zdroj:	Molecular Biology; Nov2000, Vol. 34 Issue 6, p895-901, 7p
Abstrakt:	Mercaptopurine and thioguanine are anticancer and immunosuppresive agents that exert their primary cytotoxic effects via incorporation of deoxythioguanosine into DNA. Elucidation of molecular mechanisms underlying the sensitivity/resistance to thiopurine drugs is essential to further improving the therapy for leukemia. Inherited deficiency in thiopurine S-methyltransferase activity determines idiosyncratic reactions to thiopurines. Isolation and cloning of mutant alleles from humans with thiopurine S-methyltransferase deficiency has helped to develop PCR-based genotyping assays for this disorder. Incorporation of deoxythioguanosine into DNA substantially alters DNA–protein interactions at several steps of DNA replication. Importantly, it prevents RNA hydrolysis by RNase H in the DNA–RNA heteroduplex, and decreases the thermal stability of the DNA duplexes. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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