Max Planck Research Unit for Enzymology of Protein Folding, Weinbergweg 22, 06120 Halle/Saale, Germany.
Chemistry. 2012 Aug 6;18(32):9841-8. doi: 10.1002/chem.201200863. Epub 2012 Jul 10.
The amide bond as peptide linkage plays an important role in protein structure and function. A large number of theoretical and experimental studies have focused on the specific nature of the peptide bond. Little attention, however, has been paid to their chalcogen-substituted congeners, although experimental data on thioamides revealed inconsistencies with the conventional view of amide resonance theory. Here, we employed thioxo and selenoxo substitution to determine experimentally how heavier chalcogens affect the properties of the peptide bond and adjacent atoms. NMR data revealed pronounced deshielding of heteronuclei within a three-bond distance to the chalcogen atom; this indicates an enhanced electron-withdrawing potential of the heavier chalcogens despite their lower electronegativities compared to oxygen. Interestingly, linear correlations were observed between chalcogen atomic polarizability and the chemical shift values of those neighboring heteronuclei as well as several physicochemical properties, such as electronic excitation energy, C-N rotation barrier, dipole moment and amide proton dissociation. We conclude that the chalcogen polarizability, which relates to the charge capacity, is the dominant factor that determines the electronic properties of peptide bonds substituted with heavier chalcogens.
酰胺键作为肽键在蛋白质结构和功能中起着重要作用。大量的理论和实验研究都集中在肽键的特殊性质上。然而，人们对其硫代和硒代类似物关注甚少，尽管关于硫代酰胺的实验数据与酰胺共振理论的传统观点不一致。在这里，我们采用硫代和硒代取代来实验确定较重的硫族元素如何影响肽键和相邻原子的性质。NMR 数据显示，在与硫族原子相隔三个键的距离内，杂核明显去屏蔽；这表明尽管与氧相比，较重的硫族元素的电负性较低，但它们具有更强的电子吸电性。有趣的是，观察到了硫族原子极化率与相邻杂核的化学位移值以及几个物理化学性质（如电子激发能、C-N 旋转势垒、偶极矩和酰胺质子离解）之间的线性相关性。我们得出结论，与电荷容量有关的硫族原子极化率是决定取代较重硫族元素的肽键电子性质的主导因素。
