Marine cyanobacterial fatty acid amides acting on cannabinoid receptors.
Marine cyanobacterial fatty acid amides acting on cannabinoid receptors.
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DOI：
10.1002/cbic.201200502
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发表时间：
2012-12-21
期刊：
影响因子：
3.2
通讯作者：
Luesch, Hendrik
中科院分区：
文献类型：
--
作者：
Montaser, Rana;Paul, Valerie J.;Luesch, Hendrik
脂类被不同的生物体利用，这表明这类化合物在进化上具有保守的作用。[1]事实上，由于脂类生物分子在广泛的生理功能中的关键作用，脂类组学正在成为一个关键的研究领域。[2]研究还发现了一些重要的脂类-蛋白质相互作用，其中脂类分子可以结合到特定的蛋白质结构域来调节生理效应。内源性大麻素系统是一个典型的例子，其中两个特征性的G蛋白偶联大麻素受体CB1和CB2受到内源性脂质的调节，即内源性大麻素。重要的是，这个系统已经牵涉到各种病理生理学，包括神经退行性疾病、进食障碍、疼痛、炎症和癌症。[3-7]因此，更好地了解这个系统变得非常有意义，大麻素受体被认为是不同疾病的可能靶点。[1，5]经典的概念是，在给定的GPCR中，所有激动剂都会诱导类似的下游事件，现在还不确定，最新的实验证据支持在大麻素受体上存在配体和特定的功能选择性。识别能够与大麻素受体结合的新的结构支架仍然是进一步深入研究这一复杂系统的重要工具。双胺(N-花生四烯基乙醇胺)(1)(方案1)是内源性大麻素家族中第一个被识别的内源性配体。[8]受其结构的影响，这种脂肪酸酰胺的发现表明，其他天然和合成的脂肪酸酰胺也可能作为大麻素受体配体发挥作用。在这方面，Lyngbya属的海洋蓝藻具有富含脂肪酸酰胺(除了多肽)的特征代谢特征，[9]，因此是作用于大麻素受体的新模型化合物的潜在来源。支持这一假设的是，有报道称，从Lyngbya样本中分离出的代谢物可以与大麻素受体相互作用。据我们所知，到目前为止，只有五种海洋蓝藻脂肪酸酰胺被鉴定为与大麻素受体具有结合亲和力：格拉纳达胺(2)[10]、半环胺A(3)、B和G[11]以及最近报道的代谢物丝氨酰胺A(4)[12](方案1)。然而，它们中没有一个在
Lipids are utilized by diverse organisms, which suggests an evolutionarily conserved role of this class of compounds.[1] Indeed, lipidomics is emerging as a crucial field of research because of the key role of lipid biomolecules in a wide array of physiological functions.[2] Research has also uncovered some vital lipid-protein interactions where lipid molecules can bind to specific protein domains to mediate physiological effects. The endocannabinoid system is a representative example, where two characterized G-protein coupled cannabinoid receptors CB1 and CB2 are modulated by endogenous lipids known as endocannabinoids. Importantly, this system has been implicated in various pathophysiologies, including neurodegenerative diseases, eating disorders, pain, inflammation and cancer.[3–7] Therefore, a better understanding of this system has become of significant interest, and the cannabinoid receptors have been viewed as possible targets for different diseases.[1, 5] The classical concept that all agonists at a given GPCR induce a similar repertoire of downstream events is now uncertain, and the latest experimental evidence supports the existence of ligandspecific functional selectivity at the cannabinoid receptors.[3] Consequently, the identification of new structural scaffolds that can bind to the cannabinoid receptors remains an essential tool to dig further into this complex system.Anandamide (N-arachidonoylethanolamine)(1)(Scheme 1) was the first endogenous ligand to be identified among the endocannabinoid family.[8] Influenced by its structure, the discovery of this fatty acid amide suggested that other natural and synthetic fatty acid amides might function as cannabinoid receptor ligands as well. In that context, marine cyanobacteria of the genus Lyngbya have a characteristic metabolic profile that is rich in fatty acid amides (in addition to peptides),[9] and therefore represent a potential source of new model compounds acting on the cannabinoid receptors. Support for this assumption arises from reports of metabolites isolated from Lyngbya samples that can interact with the cannabinoid receptors. To the best of our knowledge, there are only five marine cyanobacterial fatty acid amides identified to date with binding affinities to the cannabinoid receptors; grenadamide (2)[10], semiplenamides A (3), B, and G [11] and the recently reported metabolite serinolamide A (4)[12](Scheme 1). However, none of them have been tested in
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影响因子：
3.8
作者：
Montaser R;Paul VJ;Luesch H
通讯作者：
Luesch H
影响因子：
4.2
作者：
Marchalant, Yannick;Cerbai, Francesca;Wenk, Gary L.
通讯作者：
Wenk, Gary L.
影响因子：
3.4
作者：
GUNSTONE, FD;POLLARD, MR;VEDANAYAGAM, HS
通讯作者：
VEDANAYAGAM, HS
影响因子：
5.8
作者：
Bosier, Barbara;Muccioli, Giulio G.;Lambert, Didier M.
通讯作者：
Lambert, Didier M.
影响因子：
4.9
作者：
Matias, I;Bisogno, T;Di Marzo, V
通讯作者：
Di Marzo, V