Perdih Andrej, Kikelj Danijel
Faculty of Pharmacy, University of Ljubljana, Slovenia.
Curr Med Chem. 2006;13(13):1525-56. doi: 10.2174/092986706777442066.
Peptides exist in solution as an equilibrium mixture of conformers. The backbone conformational constraints are of interest as a means of limiting degrees of freedom and thereby constraining a synthetic peptide into the bioactive conformation. This concept plays an important role in the design of peptidomimetics in the drug development process. In the early eighties, Freidinger proposed the concept of protected lactam-bridged dipeptides, which was a milestone in the design of conformationally constrained peptides. These types of compounds, now widely known as Freidinger lactams, have been of interest to many medicinal and peptide chemists. This review seeks to present the various applications that Freidinger lactams and their hetero-, fused- and unsaturated analogs have found in the design of conformationally constrained peptidomimetics in different therapeutic areas.
肽在溶液中以构象异构体的平衡混合物形式存在。主链构象限制作为一种限制自由度从而将合成肽限制为生物活性构象的手段而备受关注。这一概念在药物开发过程中的肽模拟物设计中起着重要作用。在八十年代早期，弗雷丁格提出了受保护的内酰胺桥连二肽的概念，这是构象受限肽设计中的一个里程碑。这类化合物现在被广泛称为弗雷丁格内酰胺，受到了许多药物化学家和肽化学家的关注。本综述旨在介绍弗雷丁格内酰胺及其杂环、稠环和不饱和类似物在不同治疗领域的构象受限肽模拟物设计中的各种应用。
