Department of Chemistry, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
Biopolymers. 2012 Dec;97(12):1018-25. doi: 10.1002/bip.22119.
The γ-peptide β-turn structures have been designed computationally by the combination of chirospecific γ(2),(3)-residues of 2-(aminomethyl)cyclohexanecarboxylic acid (γAmc(6)) with a cyclohexyl constraint on the C(α) -C(β) bond using density functional methods in water. The chirospecific γAmc(6) dipeptide with the (2S,3S)-(2R,3R) configurations forms a stable turn structure in water, resembling a type II' turn of α-peptides, which can be used as a β-turn motif in β-hairpins of Ala-based α-peptides. The γAmc(6) dipeptide with homochiral (2S,3S)-(2S,3S) configurations but different cyclohexyl puckerings shows the capability to be incorporated into one of two β-turn motifs of gramicidin S. The overall structure of this gramicidin S analogue is quite similar to the native gramicidin S with the same patterns and geometries of hydrogen bonds. Our calculated results and the recently observed results may imply the wider applicability of chirospecific γ-peptides with a cyclohexyl constraint on the backbone to form various peptide foldamers.
γ-肽 β-转角结构是通过密度泛函方法在水中将手性特异的 2-(氨甲基)环己烷羧酸（γAmc(6)）的γ(2),(3)-残基与 C(α)-C(β)键上的环己基约束相结合而计算设计得到的。具有（2S,3S）-（2R,3R）构型的手性特异的γAmc(6)二肽在水中形成稳定的转角结构，类似于α-肽的 II' 型转角，可作为基于丙氨酸的α-肽的β-发夹中的β-转角基序。具有手性相同（2S,3S）-（2S,3S）但环己基构象不同的γAmc(6)二肽显示出能够整合到格兰菌素 S 的两种β-转角基序之一的能力。这种格兰菌素 S 类似物的整体结构与天然格兰菌素 S 非常相似，具有相同的氢键模式和几何形状。我们的计算结果和最近观察到的结果可能意味着在手性特异的γ-肽的骨架上具有环己基约束以形成各种肽折叠体的更广泛适用性。
