What makes the guanidinium cation so special?

在研究离子对蛋白质稳定性的影响时，简单的无机阳离子遵循一个重要的经验法则：阳离子的表面电荷密度越高，离子对溶液中蛋白质的不稳定性就越强。然而，体积较大的有机胍离子（Gdm+）具有较低的表面电荷密度，是最有效的蛋白质变性剂之一。因此，Gdm+是Hofmeister系列中的一个突出的例外。近年来，很明显，Gdm+对蛋白质的这种特殊作用不能用水溶液中胍电解质的体积性质来解释，而必须与Gdm+与蛋白质的特定相互作用有关。事实上，计算机模拟表明Gdm+与模型蛋白有特定的相互作用。然而，迄今为止，关于Gdm+与蛋白质相互作用的确切机制仍存在争议。研究表明，Gdm+离子与肽主链结合，与带正电或负电的蛋白质侧链相互作用，或覆盖蛋白质的疏水片段。这些相互作用机制中的每一种都被认为导致了蛋白质的展开。我们将通过实验研究Gdm+与小模型蛋白的相互作用，并测试上述不同情况。我们将测定Gdm+与疏水基团、带电荷侧链和酰胺主链的结合强度。这将揭示主要的展开机制和是什么使胍离子成为如此有效的蛋白质变性剂。

When studying the effect of ions on the stability of proteins, simple inorganic cations follow an important rule of thumb: the higher the surface charge density of the cation the stronger the ion destabilizes proteins in solution. However, the rather bulky, organic guanidinium cation (Gdm+), having a low surface charge density, is amongst the most effective protein denaturants. Thus, Gdm+ is a prominent exception in the Hofmeister series. In recent years it became apparent that this exceptional effect of Gdm+ on proteins cannot be explained from bulk properties of aqueous guanidinium electrolytes, but must be related to the specific interaction of Gdm+ with proteins.Indeed, computer simulations suggest specific interaction of Gdm+ with model proteins. However, to date the exact mechanism how Gdm+ interacts with proteins is controversially discussed. It has been suggested that Gdm+ ions bind to the peptide backbone, interact with the positively or negatively charged protein side-chains, or cover hydrophobic fragments of the proteins. Each of these interaction mechanisms is claimed to lead to the unfolding of the protein.We will study the interaction of Gdm+ with small model proteins experimentally and test the different scenarios mentioned above. We will determine the binding strength of Gdm+ to hydrophobic moieties, charged side chains, and to the amide backbone. This will reveal the predominant unfolding mechanism and what makes the guanidinium cation such an efficient protein denaturant.