DEAZA ANALOGUES OF AMETHOPTERIN (METHOTREXATE) *
DEAZA ANALOGUES OF AMETHOPTERIN (METHOTREXATE) *
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氨甲蝶呤（甲氨蝶呤）的 DEAZA 类似物 *
DOI：
10.1111/j.1749-6632.1971.tb46976.x
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发表时间：
1971
影响因子：
5.2
通讯作者：
C. Temple
中科院分区：
文献类型：
--
作者：
J. Montgomery;R. D. Elliott;Suzanne L. Straigh;C. Temple
叶酸（HI）的4-氨基-4-脱氧类似物（I和11）对二氢叶酸还原酶I-的非常强的亲和力：“其被描述为酶的“化学计量的”或“假不可逆的”抑制“，已经成为许多主题，并且已经提出了对该现象的至少三种解释。由于2，4-二氨基杂环比2-氨基-4-0x0杂环更具碱性，Baker提出二氨基化合物结合的增加是由于质子化物质与酶上的供体络合。“马修斯和Huennekens认为，结合的增加是由于氨基蝶呤与酶的一个额外的氢键，该氢键通过4-氨基形成。12 Zakrzewski提出，酶与这些化合物的2，4-二氨基嘧啶部分的四个氮官能团之间的四个氢键可以解释它们的强结合。
The very strong affinity of 4-amino-4-deoxy analogues ( I and 11) of folic acid ( H I ) for dihydrofolic reductase,l-:’ which has been described as “stoichiometric” or “pseudoirreversible” inhibition of the enzyme,’ has been the subject of numerous and at least three explanations for this phenomenon have been advanced. Since the 2,4-diamino heterocycles are more basic than the 2-amino-4-0x0 heterocycles, Baker proposed that the increase in binding of the diamino compounds is due to protonated specie complexing with a donor cite on the enzyme.x This proposal has been amplified further by Pullman and coworkers,sq l 1 and Baker has presented experimental evidence to support it.“ Mathews and Huennekens believe that the increased binding is due to one additional hydrogen bond of aminopterin to the enzyme, this hydrogen bond being formed through the 4-amino group.12 Zakrzewski suggested that four hydrogen bonds between the enzyme and the four nitrogen functions of the 2,4-diaminopyrimidine moiety of these compounds could account for their strong binding.6* lR