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首页> 外文期刊>Chemistry: A European journal >Chemistry and Biology of HPAs: A Family of Ceramide Trafficking Inhibitors
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Chemistry and Biology of HPAs: A Family of Ceramide Trafficking Inhibitors

机译：HPA的化学和生物学：神经酰胺贩运抑制剂家族。

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摘要

In 2001, two years before the disclosure of the CERT-associated Cer transfer machinery, N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl)alkanamides (HPAs) were described as the first, and to date unique, family of intracellular Cer trafficking inhibitors. The dodecanamide derivative, HPA-12, turned out to be a benchmark as a cellular inhibitor of CERT-mediated de novo sphingomyelin biosynthesis. In only 15 years after its first disclosure, this compound has prompted a growing number of biological and chemical studies. Its initial chemical development closely paralleled the study of the CERT protein. It was only after its structural revision in 2011 that HPA-12 received broad attention from the synthetic chemistry community, leading to novel analogues with enhanced protein binding. This Minireview aims at presenting an exhaustive report of the syntheses of HPA-12 and analogues. Biological activities of this CERT inhibitor and structure-activity relationships are also presented to afford a comprehensive overview of the chemistry and biology of the HPA series.
机译：在2001年，即与CERT相关的Cer转移机制公开之前的两年，N-（3-羟基-1-羟甲基-3-苯基丙基）烷酰胺（HPA）被描述为第一个也是迄今为止唯一的细胞内家族Cer贩运抑制剂。十二烷酰胺衍生物HPA-12被证明是作为CERT介导的新生鞘磷脂生物合成细胞抑制剂的基准。首次公开后仅15年，该化合物就促进了越来越多的生物学和化学研究。其最初的化学发展与CERT蛋白的研究非常相似。直到2011年对其结构进行修订后，HPA-12才受到合成化学界的广泛关注，从而产生了具有增强的蛋白质结合能力的新型类似物。这份小型审查旨在详尽地报告HPA-12和类似物的合成。还介绍了此CERT抑制剂的生物活性和构效关系，以全面概述HPA系列的化学和生物学。

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