Synthesis and evaluation of a polyamine phosphinate and phosphonamidate as transition-state analogue inhibitors of spermidine/spermine-N1-acetyltransferase.
Synthesis and evaluation of a polyamine phosphinate and phosphonamidate as transition-state analogue inhibitors of spermidine/spermine-N1-acetyltransferase.
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作为亚精胺/精胺-N1-乙酰转移酶过渡态类似物抑制剂的聚胺次膦酸盐和膦酰胺盐的合成和评价。
DOI：
10.1016/0968-0896(96)00072-7
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发表时间：
1996
影响因子：
3.5
通讯作者：
Woster,PM
中科院分区：
文献类型：
--
作者：
Wu,R;Saab,NH;Huang,H;Wiest,L;Pegg,AE;CaseroJr,RA;Woster,PM
多胺类似物如双（乙基）去甲精胺和NI-乙基-NII-[（环丙基）甲基]-4，8-二氮杂十一烷（CPENSpm）在体外作为酶亚精胺/精胺-N ′-乙酰转移酶（SSAT）的抑制剂，并且对许多细胞系具有令人印象深刻的抗肿瘤活性。然而，这些化合物在完整细胞中超诱导SSAT的倾向限制了它们在旨在阐明SSAT在细胞代谢中的作用的研究中的有用性。最近合成的烷基多胺类似物NI-乙基-NII-[（环庚基）甲基]-4，8-二氮杂十一烷（CHENSpm，3）也是SSAT的有效抑制剂，并且具有有效的抗肿瘤活性，但似乎不超诱导SSAT。这些研究结果表明，它是可能的合成多胺类似物，可用于选择性抑制酶的细胞代谢研究。沿着这些路线，合成了基于磷酸盐的过渡态类似物4和5，并将其评价为分离的SSAT的抑制剂。氨基磷酸酯4在测定条件下快速水解，因此不抑制酶。然而，次膦酸盐类似物5是纯化的人SSAT的有效抑制剂，Ki值为250 μM。还将5的抑制活性与CHENSpm（IC 50 = 13 μM）以及一系列双取代烷基多胺类似物的抑制活性进行了比较。不对称取代的多胺类似物CHENSpm（3）和次膦酸盐过渡态类似物5代表了第一个功能性的、非超诱导的人SSAT抑制剂。
Polyamine analogues such as bis(ethyl)norspermine and NI-ethyl-NII-[(cyclopropyl)methyl]-4,8-diazaundecane (CPENSpm) act as inhibitors of the enzyme spermidine/spermine-N′-acetyltransferase (SSAT) in vitro and possess impressive antitumor activity against a number of cell lines. However, the propensity of these compounds to superinduce SSAT in intact cells limits their usefulness in studies aimed at elucidating the role of SSAT in cellular metabolism. The recently synthesized alkylpolyamine analogue NI-ethyl-NII-[(cycloheptyl)methyl]-4,8-diazaundecane (CHENSpm, 3) is also an effective inhibitor of SSAT and has potent antitumor activity, but does not appear to superinduce SSAT. These findings suggest that it is possible to synthesize polyamine analogues that can be used for selective inhibition of the enzyme in cellular metabolic studies. Along these lines, the phosphate-based transition state analogues 4 and 5 were synthesized and evaluated as inhibitors of isolated SSAT. Phosphonamidate 4 was rapidly hydrolyzed under the assay conditions, and thus did not inhibit the enzyme. However, the phosphinate analogue 5 was an effective inhibitor of purified human SSAT, with a Kivalue of 250 μM. The inhibitory activity of 5 was also compared with that of CHENSpm (IC50= 13 μM), as well as a series of bis-substituted alkylpolyamine analogues. The unsymmetrically substituted polyamine analogue CHENSpm (3) and the phosphinate transition state analogue 5 represent the first functional, nonsuperinducing inhibitors of human SSAT.
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α-二氟甲基鸟氨酸（鸟氨酸脱羧酶抑制剂）和 N1,N8-双（乙基）亚精胺（该酶的明显调节剂）对 L1210 细胞生长抑制的比较和表征。
影响因子：
11.2
作者：
Porter,CW;Ganis,B;Vinson,T;Marton,LJ;Kramer,DL;Bergeron,RJ
通讯作者：
Bergeron,RJ
人亚精胺/精胺 N1-乙酰转移酶在大肠杆菌中表达的影响。
影响因子：
2.9
作者：
Parry,L;Lopez-Ballester,J;Wiest,L;Pegg,AE
通讯作者：
Pegg,AE
用四氯化碳处理的大鼠肝脏中亚精胺 N-乙酰转移酶的特性及其在亚精胺转化为腐胺中的作用。
DOI：
--
发表时间：
1981
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Matsui,I;Wiegand,L;Pegg,AE
通讯作者：
Pegg,AE
影响因子：
4.1
作者：
CASERO, RA;CELANO, P;PEGG, AE
通讯作者：
PEGG, AE
影响因子：
7.3
作者：
SAAB, NH;WEST, EE;WOSTER, PM
通讯作者：
WOSTER, PM