Marshall G R, Hodgkin E E, Langs D A, Smith G D, Zabrocki J, Leplawy M T
Department of Pharmacology, Washington University School of Medicine, Saint Louis, MO 63110.
Proc Natl Acad Sci U S A. 1990 Jan;87(1):487-91. doi: 10.1073/pnas.87.1.487.
The presence of multiple alpha,alpha-dialkyl amino acids such as alpha-methylalanine (alpha-aminoisobutyric acid, Aib) leads to predominantly helical structures, either with alpha-helical or 3(10)-helical hydrogen bonding patterns. The crystal structure of emerimicin-(1-9) benzyl ester (Ac-Phe-Aib-Aib-Aib-Val-Gly-Leu-Aib-Aib-OBzl) reported here shows essentially pure alpha-helical character, whereas other similar compounds show predominantly 3(10)-helical structures. The factors that govern helical preference include the inherent relative stability of the alpha-helix compared with the 3(10)-helix, the extra hydrogen bond seen with 3(10)-helices, and the enhanced electrostatic dipolar interaction of the 3(10)-helix when packed in a crystalline lattice. The balance of these forces, when combined with the steric requirements of the amino acid side chains, determines the relative stability of the two helical conformations under a given set of experimental conditions.
多个α,α-二烷基氨基酸（如α-甲基丙氨酸（α-氨基异丁酸，Aib））的存在会导致主要形成螺旋结构，具有α-螺旋或3(10)-螺旋氢键模式。本文报道的埃默里霉素-(1-9)苄酯（Ac-Phe-Aib-Aib-Aib-Val-Gly-Leu-Aib-Aib-OBzl）的晶体结构显示出基本纯的α-螺旋特征，而其他类似化合物则主要呈现3(10)-螺旋结构。决定螺旋偏好的因素包括α-螺旋与3(10)-螺旋相比的固有相对稳定性、3(10)-螺旋中额外的氢键，以及3(10)-螺旋在晶格中堆积时增强的静电偶极相互作用。当这些力与氨基酸侧链的空间需求相结合时，在给定的一组实验条件下决定了两种螺旋构象的相对稳定性。
