Balaji V N, Ramnarayan K, Chan M F, Rao S N
ImmunoPharmaceutics, Inc., San Diego, CA.
Pept Res. 1994 Mar-Apr;7(2):60-71.
The design of metabolically stable, conformationally constrained peptidomimetics is an increasingly used approach in developing orally active drug candidates in pharmaceutical research. In this paper we present conformational energy calculations on model compounds containing 1-aminocyclopropane carboxylic acid (ACC) and its derivatives using molecular mechanics methods. The low energy models adopt conformations characteristic of a variety of regular structures such as the alpha-helix, gamma-turn and three- and fourfold helices. The energetically most favored models adopt either the left- or right-handed 2.2(7) helical conformation or the gamma-turn. These results are qualitatively consistent with the crystal structures of peptide analogs containing ACC and have potential implications for the design of peptidomimetics where the conformational features characteristic of a specific type of gamma-turn are desired.
在药物研究中，设计代谢稳定、构象受限的肽模拟物是开发口服活性候选药物时越来越常用的方法。在本文中，我们使用分子力学方法对含有1-氨基环丙烷羧酸（ACC）及其衍生物的模型化合物进行了构象能量计算。低能量模型采用多种规则结构的特征构象，如α-螺旋、γ-转角以及三股和四股螺旋。能量上最有利的模型采用左手或右手2.2(7)螺旋构象或γ-转角。这些结果在定性上与含有ACC的肽类似物的晶体结构一致，并且对于设计需要特定类型γ-转角特征构象的肽模拟物具有潜在意义。
