Cody V, Sutton P A
Medical Foundation of Buffalo, Inc., New York 14203.
Anticancer Drug Des. 1987 Dec;2(3):253-62.
The results of crystal structure determinations on a series of protonated N1-phenyl-substituted 1,2-dihydro-2,2-dimethyl-4,6-diamino-s-triazine anti-cancer antifolates show that the s-triazine ring adopts a twist-sofa conformation with C2 nearly 0.5 A above the plane and the N1-phenyl ring is nearly perpendicular to the s-triazine ring, in agreement with minimum energy calculations and with antifolate binding in the active site of chicken liver dihydrofolate reductase. The 2,2-dimethyl groups are equatorial and axial. Comparison of these s-triazines with analogous pyrimidine antifolates reveals that the axial 2-methyl group occupies the same conformational space as the 6-methyl group in active anti-cancer agents.
一系列质子化的N1-苯基取代的1,2-二氢-2,2-二甲基-4,6-二氨基-s-三嗪抗癌抗叶酸剂的晶体结构测定结果表明，s-三嗪环采取扭曲沙发构象，C2在平面上方近0.5 Å，N1-苯基环几乎垂直于s-三嗪环，这与最低能量计算结果以及在鸡肝二氢叶酸还原酶活性位点的抗叶酸结合情况一致。2,2-二甲基基团分别处于平伏键和直立键。将这些s-三嗪与类似的嘧啶抗叶酸剂进行比较发现，直立的2-甲基基团与活性抗癌剂中的6-甲基基团占据相同的构象空间。
