人DNA甲基转移酶（DNMT）酶抑制剂（l）-S-腺苷-l-高半胱氨酸周围的立体化学。
SAR around (l)-S-adenosyl-l-homocysteine, an inhibitor of human DNA methyltransferase (DNMT) enzymes.
作者信息
Saavedra Oscar M, Isakovic Ljubomir, Llewellyn David B, Zhan Lijie, Bernstein Naomy, Claridge Stephen, Raeppel Franck, Vaisburg Arkadii, Elowe Nadine, Petschner Andrea J, Rahil Jubrail, Beaulieu Norman, MacLeod A Robert, Delorme Daniel, Besterman Jeffrey M, Wahhab Amal
机构信息
MethylGene Inc., Departments of Medicinal Chemistry, Montreal, Quebec, Canada.
出版信息
Bioorg Med Chem Lett. 2009 May 15;19(10):2747-51. doi: 10.1016/j.bmcl.2009.03.113. Epub 2009 Mar 28.
The inhibitory activity of base-modified SAH analogues and the specificity of inhibiting human DNMT1 and DNMT3b2 enzymes was explored. The 6-amino group was essential while the 7-N of the adenine ring of SAH could be replaced by CH- without loss of activity against both enzymes. The introduction of small groups at the 2-position of the adenine moiety favors DNMT1 over DNMT3b2 inhibition whereas alkylation of the N(6)-amino moiety favors the inhibition of DNMT3b2 enzyme.
研究了碱基修饰的SAH类似物的抑制活性以及对人DNMT1和DNMT3b2酶抑制的特异性。6-氨基基团至关重要，而SAH腺嘌呤环的7-N可以被CH-取代，而不会丧失对这两种酶的活性。在腺嘌呤部分的2-位引入小基团有利于对DNMT1的抑制而非DNMT3b2，而N(6)-氨基部分的烷基化则有利于对DNMT3b2酶的抑制。
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