Biondi Barbara, Formaggio Fernando, Toniolo Claudio, Peggion Cristina, Crisma Marco
CNR - Institute of Biomolecular Chemistry, Padova Unit, Padova, Italy.
Department of Chemical Sciences, University of Padova, Padova, Italy.
J Pept Sci. 2025 Jul;31(7):e70036. doi: 10.1002/psc.70036.
The results of an analysis on the presence of π-turns, characterized by an i ← i + 5 C=O···H-N intramolecular hydrogen bond, in the X-ray diffraction structures of peptides are discussed. The survey returned a total of 55 π-turn occurrences in linear and cyclic peptides. π-Turns characterized by a helical conformation for residue i + 4, but with a screw sense opposite to that of the three preceding residues, are largely prevailing. They are often found at the C-end of incipient or fully developed α-helices, 3-helices, and mixed α-/3-helices, thus acting as a C-capping motif. However, the structures of two linear peptides and 15 cyclopeptides indicate that these types of π-turns can exist in isolation, without the support of a preceding helix. The frequent presence of additional intramolecular hydrogen bonds internal to the π-turn is also investigated. Cyclopeptides offered examples of two types of π-turns that have no parallel in the structures of proteins. Differently from proteins, π-turns characterized by helical ϕ, ψ sets of the same screw sense for all internal residues are hitherto unreported in the X-ray diffraction structures of peptides. A suggestion for the rational design in peptides/peptidomimetics of a π-turn featuring the screw-sense reversal of residue i + 4 is proposed.
本文讨论了在肽的X射线衍射结构中，以i←i + 5 C=O···H-N分子内氢键为特征的π-转角存在情况的分析结果。该调查共发现线性和环状肽中存在55个π-转角。以残基i + 4呈螺旋构象但螺旋方向与前三个残基相反为特征的π-转角占主导地位。它们常出现在初始或完全形成的α-螺旋、3-螺旋和混合α-/3-螺旋的C端，因此起到C端封端基序的作用。然而，两种线性肽和15种环肽的结构表明，这些类型的π-转角可以独立存在，无需前面螺旋的支撑。还研究了π-转角内部频繁出现的额外分子内氢键。环肽提供了两种在蛋白质结构中不存在的π-转角实例。与蛋白质不同，肽的X射线衍射结构中迄今尚未报道所有内部残基具有相同螺旋方向的螺旋ϕ、ψ集特征的π-转角。本文提出了在肽/肽模拟物中合理设计具有残基i + 4螺旋方向反转特征的π-转角的建议。
