DIFFERENTIATION-INDUCING FACTOR FROM THE SLIME-MOLD DICTYOSTELIUM-DISCOIDEUM AND ITS ANALOGS - SYNTHESIS, STRUCTURE AND BIOLOGICAL-ACTIVITY
DIFFERENTIATION-INDUCING FACTOR FROM THE SLIME-MOLD DICTYOSTELIUM-DISCOIDEUM AND ITS ANALOGS - SYNTHESIS, STRUCTURE AND BIOLOGICAL-ACTIVITY
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DOI：
10.1042/bj2560023
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发表时间：
1988-11-15
影响因子：
4.1
通讯作者：
KAY, RR
中科院分区：
文献类型：
--
作者：
MASENTO, MS;MORRIS, HR;KAY, RR
先前的工作已经导致鉴定了一类新的效应分子[DIFs（分化诱导因子）1-3]从粘菌盘状盘状体释放。这些物质可诱导盘状盘基骨柱的茎细胞分化，并被认为是在发育过程中形成柄前/孢子前模式的形态形成因子。dif是苯基烷烃-1，苯环上有氯、羟基和甲氧基取代。DIFs 1-3和它们的一些类似物已经用一个简单的两步法合成，并且每个类似物都用m.s， uv和n.m.r光谱进行了表征。研究了合成DIF-1[1-（3,5-二氯-2,6-二羟基-4-甲氧基苯基）己烷-1- 1]的晶体结构。每种类似物的特定生物活性是在生物测定中确定的，其中分离的变形虫盘基骨柱被诱导分化为柄细胞。主要生物活性物质DIF-1对茎细胞的分化率为1.8倍，达到50%。真空度M;C4烷基同源物（DIF-2）和C6烷基同源物（DIF-1）的活性分别为40%和16%。烷基链长度的进一步增加或减少会导致比活性的显著降低。苯环上的取代模式是生物活性的主要决定因素，因为2,4-二羟基-6-甲氧基和三羟基类似物的比活性低于DIF-1的1%。溴代DIF-1对生物活性影响不大；而单氯dif -1 （DIF-3）活性降低。没有证据表明DIF-1与其任何类似物之间存在拮抗或协同作用。这一系列类似物将有助于进一步研究DIF-1的生物学效应和作用方式。
Previous work has led to the identification of a novel class of effector molecules [DIFs (differentiation-inducing factors) 1-3] released from the slime mould Dictyostelium discoideum. These substances induce stalk-cell differentiation in Dictyostelium discoideum and are thought to act as morphogens in the generation of the prestalk/prespore pattern during development. The DIFs are phenylalkan-1-ones, with chloro, hydroxy and methoxy substitution on the benzene ring. DIFs 1-3 and a number of their analogues have been synthesized by using a simple two-step procedure, and each analogue has been characterized by m.s., u.v. and n.m.r. spectroscopy. The crystal structure of synthetic DIF-1 [1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)hexan-1-one, was investigated. The specific biological activity of each analogue was determined in a bioassay, where isolated Dictyostelium amoebae are induced to differentiate into stalk cells. The major biologically active substance, DIF-1, caused 50% stalk-cell differentiation at 1.8 .times. 10-10 M; the C4 alkyl homologue (DIF-2) and C6 homologue possessed 40 and 16% of the activity of DIF-1 respectively. Further increase or decrease in the alkyl chain length resulted in a marked decrease in specific activity. The pattern of substitution on the benzene ring is a major determinant of bioactivity, since the specific activities of the 2,4-dihydroxy-6-methoxy and trihydroxy analogues were less than 1% of that of DIF-1. Substitution of bromine in DIF-1 had little effect on bioactivity; in contrast the activity of monochloro-DIF-1 (DIF-3) was diminished. There was no evidence for antagonism or synergy between DIF-1 and any of its analogues. This series of analogues will facilitate further studies in the biological effects and mode of action of DIF-1.