摘要：

Strong hydrophobic bonding to dihydrofolic reductase has been observed by alkyl groups attached to the 5-position of pyrimidines or the 1-position of 1,2-dihydro- s -triazines. Studies were made with alkyl substituted 2,6-diamino-4-pyrimidinols (series A ), 2-amino-6-methyl-4-pyrimidinols (series B ), 2,4,6-triaminopyrimidines (series C ), 2,4-diamino-6-methylpyrimidines (series D ), and 4,6-diamino-1,2-dihydro-2,2-dimethyl- s -triazines (series E ); 19 different alkyl, aryl, or aralkyl groups were investigated, but not in all series. Maximum hydrophobic bonding by an n -alkyl group was reached with n -butyl in all except series B ; the B series required an n -amyl group. In all series, a further increment in binding over n -butyl was observed in the isoamyl group; the latter gave as good or better binding than the phenylpyrimidines or s -triazines of the pyrimethamine type. The butyl is probably complexed in a skew conformation. It is proposed that the 5-phenyl group of a pyrimidine or 1-phenyl group of 1,2-dihydro- s -triazine may also bind to dihydrofolic reductase by hydrophobic bonding. These observations on hydrophobic bonding can account for most of the discrepancies in increments of binding observed with the pyrimidines and dihydro- s -triazines in earlier papers. The possible uses of hydrophobic bonding to dihydrofolic reductase for species specificity are discussed.

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