A pump–probe approach was designed to determine the internal proton transfer (PT) rate in a series of poly-peptide radical cations containing both histidine and tryptophan. The proton transfer is driven by the gas-phase basicity difference between residues. The fragmentation scheme indicates that the gas-phase basicity of histidine is lower than that of radical tryptophan so that histidine is always pulling the proton away from tryptophan. However, the proton transfer requires the two basic sites to be in close proximity, which is rate limited by the peptide conformational dynamics. PT rate measurements were used to probe and explore the peptide conformational dynamics in several poly-glycines/prolines/alanines. For small and unstructured peptides, the PT rate decreases with the size, as expected from a statistical point of view in a flat conformational space. Conversely, if structured conformations are accessible, the structural flexibility of the peptide is decreased. This slows down the occurrence of conformations favorable to proton transfer. A dramatic decrease in the PT rates was observed for peptides HA_nW, when n changes from 5 to 6. This is attributed to the onset of a stable helix for n = 6. No such discontinuity is observed for poly-glycines or poly-prolines. In HA_nW, the gas-phase basicity and helix propensity compete for the position of the charge. Interestingly, in this competition between PT and helix formation in HA₆W, the energy gain associated with helix formation is large enough to slow down the PT beyond experimental time but does not ultimately prevail over the proton preference for histidine.

中文翻译：

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二级结构对多肽内部质子转移的影响


泵-探针方法旨在确定一系列含有组氨酸和色氨酸的多肽自由基阳离子的内部质子转移（PT）速率。质子转移是由残留物之间的气相碱度差驱动的。断裂方案表明组氨酸的气相碱度低于自由基色氨酸的气相碱度，因此组氨酸总是将质子从色氨酸中拉开。然而，质子转移需要两个基本位点非常接近，这受到肽构象动力学的速率限制。 PT 速率测量用于探测和探索几种聚甘氨酸/脯氨酸/丙氨酸中的肽构象动力学。对于小且非结构化的肽，PT 率随着大小而降低，正如从平坦构象空间中的统计角度所预期的那样。相反，如果可以接近结构化构象，则肽的结构灵活性就会降低。这减缓了有利于质子转移的构象的出现。当 n 从 5 变为 6 时，观察到肽 HA _n W 的 PT 速率急剧下降。这归因于 n = 6 时稳定螺旋的开始。对于聚甘氨酸或多聚甘氨酸，没有观察到这种不连续性。脯氨酸。在 HA _n W 中，气相碱度和螺旋倾向竞争电荷的位置。有趣的是，在 HA ₆ W 中 PT 和螺旋形成之间的竞争中，与螺旋形成相关的能量增益足够大，足以在实验时间之外减慢 PT，但最终不会战胜质子对组氨酸的偏好。