Gas-Phase Deprotonation of the Peptide Backbone for Tripeptides and Their Methyl Esters with Hydrogen and Methyl Side Chains
Gas-Phase Deprotonation of the Peptide Backbone for Tripeptides and Their Methyl Esters with Hydrogen and Methyl Side Chains
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DOI：
10.1021/jp3113528
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发表时间：
2012-12-27
影响因子：
3.3
通讯作者：
Cassady, Carolyn J.
中科院分区：
文献类型：
--
作者：
Bokatzian-Johnson, Samantha S.;Stover, Michele L.;Cassady, Carolyn J.
通过傅里叶变换离子回旋共振质谱仪中的质子转移反应和G3(MP2)分子轨道理论计算，获得了六种三肽（GlyGlyGly、GlyAlaGly、AlaGlyAla、AlaAlaAla、AibAibAib和SarSarSar）及其甲酯的气相酸度（GA）。所有六种肽的 GA 范围均为 321.0-323.7 kcal/mol。它们的去质子化产生 [M - H](-) 发生在 C 末端羧酸基团处。三肽的酸性比甘氨酸 (Gly) 和丙氨酸 (Ala) 的酸性高约 10 kcal/mol。这与三肽结构中发现的广泛氢键一致。对于甲酯，去质子化发生在肽主链处。 G3(MP2) 计算表明，最有利的去质子化位点是酰胺氮，通常优选中心酰胺。氮去质子化需要比亚甲基碳去质子化少 10-20 kcal/mol 的能量。只有三种甲酯（GlyGlyGly-OMe、GlyAlaGly-OMe 和 AlaAlaAla-OMe）通过电喷雾电离实验去质子化。这些酯的实验 GA 范围为 336.7-338.1 kcal/mol，与计算的 G3(MP2) 值非常一致。其他三种甲酯（AlaGlyAla-OMe、AibAibAib-OMe 和 SarSarSar-OMe）无法获得实验 GA，因为它们没有产生足够的去质子化分子离子。三肌氨酸甲酯，SarSarSar-OMe，不能在中心酰胺氮处去质子化，因为这些位点存在甲基；因此，它具有 350.6 kcal/mol 的高 G3(MP2) GA 值（酸性较低），可用于 N 末端氮的去质子化。对于 AlaGlyAla-OMe 和 AibAibAib-OMe，范德华力和溶剂可及表面的计算表明甲基阻碍了酰胺氮位点。因此，构象和空间位阻效应限制了这些肽甲酯在质谱仪中去质子化的能力。
The gas-phase acidities (GAs) of six tripeptides (GlyGlyGly, GlyAlaGly, AlaGlyAla, AlaAlaAla, AibAibAib, and SarSarSar) and their methyl esters were obtained by proton transfer reactions in a Fourier transform ion cyclotron resonance mass spectrometer and G3(MP2) molecular orbital theory calculations. All six peptides have GAs in the range 321.0-323.7 kcal/mol. Their deprotonation to produce [M - H](-) occurs at the C-terminal carboxylic acid group. The tripeptides are about 10 kcal/mol more acidic than the amino acids glycine (Gly) and alanine (Ala). This is consistent with the extensive hydrogen bonding that was found in the tripeptide structures. For the methyl esters, deprotonation occurs at the peptide backbone. G3(MP2) calculations show that the most energetically favored site of deprotonation is an amide nitrogen, with the central amide being generally preferred. Nitrogen deprotonation requires 10-20 kcal/mol less energy than deprotonation at a methylene carbon. Only three of the methyl esters (GlyGlyGly-OMe, GlyAlaGly-OMe, and AlaAlaAla-OMe) deprotonate experimentally by electrospray ionization. Experimental GAs for these esters are in the range of 336.7-338.1 kcal/mol, in excellent agreement with the calculated G3(MP2) values. Experimental GAs could not be obtained for the other three methyl esters (AlaGlyAla-OMe, AibAibAib-OMe, and SarSarSar-OMe) because they did not produce sufficient deprotonated molecular ions. Trisarcosine methyl ester, SarSarSar-OMe, cannot be deprotonated at a central amide nitrogen because methyl groups are present at these sites; consequently, it has a high G3(MP2) GA value (less acidic) of 350.6 kcal/mol for deprotonation at the N-terminal nitrogen. For AlaGlyAla-OMe and AibAibAib-OMe, calculations of van der Waals and solvent accessible surfaces reveal that methyl groups are blocking the amide nitrogen sites. Therefore, conformational and steric hindrance effects are limiting the ability of these peptide methyl esters to deprotonate in the mass spectrometer.