ICB, Padova Unit, CNR, Department of Chemistry, University of Padova, 35131 Padova, Italy.
Org Biomol Chem. 2012 Mar 28;10(12):2413-21. doi: 10.1039/c2ob06863j. Epub 2012 Feb 14.
The fully-extended, multiple C(5), conformation or 2.0(5) helix is a very appealing peptide secondary structure, in particular for its potential use as a molecular spacer, as it is characterized by the longest elevation (as high as 3.62 Å) between the α-carbon atoms of two consecutive α-amino acids. Despite this intriguing property, however, it is only poorly investigated and understood. Here, using a complete series of C(α,α)-diethylglycine (Deg) homo-oligopeptide esters to the pentamer level, we exploited the properties of a fluorophore and a quencher, synthetically positioned at the N- and C-termini of the main chain, respectively, to check the applicability of the fully-extended conformation as a rigid molecular spacer. The fluorescence study was complemented by FT-IR absorption and NMR conformational investigations. The X-ray diffraction structures of selected compounds are also reported. Unfortunately, we find that, even in a solvent of low polarity, such as chloroform, in this peptide series an equilibrium does take place between the fragile fully-extended conformation and the 3(10)-helical structure, the latter becoming more and more stable as the main chain is elongated. Since the Deg homo-peptide esters lacking any terminal aromatic group, previously investigated, are known to adopt a stable fully-extended conformation in chloroform solution, we tend to attribute the 3D-structure instability observed in this work to the presence of multiple aromatic rings in their blocking groups.
完全伸展的多 C(5)构象或 2.0(5)螺旋是一种非常吸引人的肽二级结构，特别是因为它作为分子间隔物具有潜在的用途，因为它的特征是两个连续的α-氨基酸的α-碳原子之间的最高提升（高达 3.62Å）。然而，尽管具有这种有趣的特性，但它的研究和理解还很差。在这里，我们使用一系列完全伸展的 C(α,α)-二乙基甘氨酸 (Deg)同聚肽酯到五聚体水平，利用荧光团和猝灭剂的性质，分别在主链的 N-和 C-末端进行了合成定位，以检查完全伸展构象作为刚性分子间隔物的适用性。荧光研究得到了 FT-IR 吸收和 NMR 构象研究的补充。还报告了选定化合物的 X 射线衍射结构。不幸的是，我们发现，即使在低极性溶剂（如氯仿）中，在这个肽系列中，脆弱的完全伸展构象和 3(10)-螺旋结构之间确实会发生平衡，随着主链的延长，后者变得越来越稳定。由于以前研究过的缺乏任何末端芳基基团的 Deg 同肽酯在氯仿溶液中被认为采用稳定的完全伸展构象，我们倾向于将本工作中观察到的 3D 结构不稳定性归因于其封端基团中存在多个芳环。
