Kumar Ritesh, Srivastava Richa, Singh Ramendra Kumar, Surolia Avadhesha, Rao Desirazu N
Department of Biochemistry, Indian Institute of Science, Banglore 560012, India.
Bioorg Med Chem. 2008 Mar 1;16(5):2276-85. doi: 10.1016/j.bmc.2007.11.075. Epub 2007 Dec 3.
The inhibition of methyltransferases is currently of high interest, particularly in the areas of microbial infection and cell proliferation, as there have been serious attempts to develop novel anti-microbial agents. In the present investigation, a series of 11 S-adenosyl-l-homocysteine analogues have been synthesized and effect of these analogues on DNA methylation catalyzed by DNA methyltransferases was studied. It was found that, while 5'-S-(propionic acid)5'-deoxy-9-(1'-beta-d-ribofuranosyl)1,3-dideazaadenine was an activator of EcoP15I and HhaI DNA methyltransferases, 5'-S-(propionic acid)5'-deoxy-9-(1'-beta-dribofuranosyl)adenine inhibited the methyltransferases in a non-competitive manner. An understanding of the binding of analogues to DNA methyltransferases will greatly assist the design of novel anti-microbial compounds.
甲基转移酶的抑制作用目前备受关注，尤其是在微生物感染和细胞增殖领域，因为人们一直在认真尝试开发新型抗菌剂。在本研究中，合成了一系列11种S-腺苷-L-高半胱氨酸类似物，并研究了这些类似物对DNA甲基转移酶催化的DNA甲基化的影响。结果发现，虽然5'-S-(丙酸)5'-脱氧-9-(1'-β-D-呋喃核糖基)1,3-二氮杂腺嘌呤是EcoP15I和HhaI DNA甲基转移酶的激活剂，但5'-S-(丙酸)5'-脱氧-9-(1'-β-D-呋喃核糖基)腺嘌呤以非竞争性方式抑制甲基转移酶。了解类似物与DNA甲基转移酶的结合将极大地有助于新型抗菌化合物的设计。
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