Synthesis and biological testing of cell-permeant NAADP

细胞通过化学信使与其他细胞和内部进行交流。这些信使是分子，并表现出使它们能够被专门的受体或生物信息中心唯一识别的特征。信使是在细胞膜内对外界刺激作出反应，但不能从外界穿过或穿过。这是因为细胞被一层膜包裹，这层膜将内容物保持在细胞内，而将潜在的污染物保持在细胞外。我们感兴趣的信使分子，增加细胞内的钙水平，称为NAADP。钙水平的变化是什么驱使你的心脏收缩，你的手臂肌肉收缩，以提高一个杯子到你的嘴，甚至在你的大脑细胞互相交谈。目前还没有人确定NAADP是否有效，所以我们想把它放进细胞中并找出答案。这种信使分子不会自然地穿过细胞膜，所以目前的技术水平涉及破坏细胞膜然后重建它。这是困难的，需要专业技能。我们建议尝试一种不同的，更微妙的方法，通过掩盖分子的外观，使其可以通过膜滑动。一旦进入，分子就会脱掉它的面具，恢复它的外观并提供它的信息。让NAADP悄悄地穿过细胞膜将为我们提供关于这种信使如何在不同细胞中工作的新信息。这种新方法的成功开发将使更多的科学家能够研究这种迷人的分子。

Cells communicate with other cells and internally via chemical messengers. These messenger are molecules and exhibit features that make them uniquely recognizable to specialised receptors, or biological message centres. Messengers are made inside the cell membrane in response to outside stimuli, but cannot cross to or from the outside. This is because cells are enveloped by a membrane which keeps the contents in and potential contaminants outside. We are interested in a messenger molecule that increases calcium levels inside cells, called NAADP. Changes in calcium levels is what drives your heart to contract, your arm muscle to contract to raise a cup to your mouth and even the cells in your brain to talk to each other. Nobody is yet sure NAADP is working, so we want to get it into cells and find out. This messenger molecule does not naturally cross the cell membrane, so current state of the art techniques involve destroying the membrane then rebuilding it. This is difficult and requires specialised skills. We propose to try a different, more subtle approach by masking the molecules appearance, so that it can slip through the membrane. Once inside, the molecule sheds its mask, regains its appearance and provides its message. Getting NAADP across the cell membrane by stealth will provide us with new information about how this messenger works in different cells. Successful development of this new method will allow many more scientists to study this fascinating molecule.