Baillon J G, Kolb M, Mamont P S
Merrell Dow Research Institute, Strasbourg, France.
Eur J Biochem. 1989 Jan 15;179(1):17-21. doi: 10.1111/j.1432-1033.1989.tb14515.x.
A number of N-alkylated-1,3-diaminopropane derivatives [H2N-(CH2)3-NH-(CH2)nH, where n = 1-9] have been tested as potential inhibitors of partially purified rat hepatoma (HTC) cell or pure bovine spleen spermine synthase. Among the compounds described in this paper, the most potent competitive inhibitor of spermine synthase, with respect to spermidine, is N-butyl-1,3-diaminopropane with Ki values of 11.9 nM and 10.4 nM for the HTC cell and bovine spleen enzymes respectively. Inhibition of spermine synthase by this alkylated amine is selective since spermidine synthase activity is not affected up to 100 microM N-butyl-1,3-diaminopropane at a range of 5-200 microM putrescine. Added to the culture medium of growing HTC cells, N-butyl-1,3-diaminopropane causes the expected changes in the polyamine levels with a marked decrease of spermine and an increase of spermidine. Under these conditions cell growth continues unabated. Such N-alkylated-1,3-diaminopropane derivatives may have considerable potential as tools for studying the role of polyamines and in particular the functions of spermine in cell multiplication and differentiation.
已对多种N-烷基化-1,3-二氨基丙烷衍生物[H2N-(CH2)3-NH-(CH2)nH，其中n = 1-9]作为部分纯化的大鼠肝癌(HTC)细胞或纯牛脾脏精胺合酶的潜在抑制剂进行了测试。在本文所述的化合物中，就亚精胺而言，最有效的精胺合酶竞争性抑制剂是N-丁基-1,3-二氨基丙烷，其对HTC细胞和牛脾脏酶的Ki值分别为11.9 nM和10.4 nM。这种烷基化胺对精胺合酶的抑制具有选择性，因为在5-200 microM腐胺范围内，高达100 microM的N-丁基-1,3-二氨基丙烷不会影响亚精胺合酶的活性。将N-丁基-1,3-二氨基丙烷添加到生长中的HTC细胞的培养基中，会导致多胺水平发生预期变化，精胺显著减少，亚精胺增加。在这些条件下，细胞生长持续不受影响。此类N-烷基化-1,3-二氨基丙烷衍生物作为研究多胺的作用，特别是精胺在细胞增殖和分化中的功能的工具，可能具有相当大的潜力。
