SYNTHESIS AND PHOTOCHEMISTRY OF PHOTOLABILE N-GLYCINE DERIVATIVES AND EFFECTS OF ONE ON THE GLYCINE RECEPTOR
SYNTHESIS AND PHOTOCHEMISTRY OF PHOTOLABILE N-GLYCINE DERIVATIVES AND EFFECTS OF ONE ON THE GLYCINE RECEPTOR
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DOI：
10.1021/bi00139a011
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发表时间：
1992-06-23
期刊：
影响因子：
2.9
通讯作者：
HESS, GP
中科院分区：
文献类型：
--
作者：
BILLINGTON, AP;WALSTROM, KM;HESS, GP
合成了三种甘氨酸的光敏性前体，它们含有附着在氨基上的光敏性2-硝基苯段。当暴露在308 ~ 350 nm的紫外线下时，化合物光解释放甘氨酸，甘氨酸是中枢神经系统中一种重要的抑制性神经递质。甘氨酸作为光解产物的鉴定采用两种不同的方法：采用薄层色谱法分离光解样品，然后与茚三酮反应；采用Waters微标签法结合高效液相色谱法识别衍生化甘氨酸。研究了这些化合物在22℃下的光解反应，并测量了反应中一种瞬态中间体的衰变速率，该速率被认为反映了产物的释放。对于N-（α -羧基-2-硝基苄基）甘氨酸，在pH 6.8和pH 7.5下的衰变速率分别为940 s-1和600 s-1。此外，该化合物被发现在光解时表现出生物活性；用培养的含有神经元甘氨酸受体的小鼠脊髓细胞检测甘氨酸的释放。这里采用的方法有助于证明神经递质光降解前体的效用，这些前体的保护基团通过氨基与神经递质相连。这类化合物的快速光解释放游离神经递质对神经递质受体的化学动力学研究具有重要意义。以前，这类研究受到限制，因为可用的神经递质传递方法没有给出足够高的时间分辨率。
Three photolabile precursors of glycine containing a photosensitive 2-nitrobenzyl moiety attached to the amino group have been synthesized. When exposed to ultraviolet radiation between 308 and 350 nm, the compounds photolyze to release glycine, an important inhibitory neurotransmitter in the central nervous system. The identification of glycine as a photolysis product was determined by two different methods: separation of the photolyzed sample by thin-layer chromatography followed by a reaction with ninhydrin, and recognition of derivatized glycine using the Waters pico-tag method in conjunction with high-performance liquid chromatography. The photolysis of these compounds at 22-degrees-C has been investigated, and the rate of decay of a transient intermediate in the reaction, which is assumed to reflect product release, has been measured. For N-(alpha-carboxy-2-nitrobenzyl)glycine this decay rate was found to be 940 s-1 at pH 6.8 and 600 s-1 at pH 7.5. Additionally, this compound was found to exhibit biological activity upon photolysis; cultured mouse spinal cord cells containing neuronal glycine receptors were used to detect the glycine liberation. The approach adopted here is useful in demonstrating the utility of photolabile precursors of neurotransmitters that have the protecting group linked to the neurotransmitter through the amino group. The rapid photolysis of such compounds to release free neurotransmitter is valuable in gaining access to chemical kinetic studies of neurotransmitter receptors. Previously, such studies have been limited because the available methods for neurotransmitter delivery did not give a sufficiently high time resolution.