Département de Chimie, Université de Montréal, CP 6128, Succursale Centre Ville, Montréal, Québec, H3C3J7, Canada.
Future Med Chem. 2011 Jul;3(9):1139-64. doi: 10.4155/fmc.11.74.
Azapeptides are peptide analogs in which one or more of the amino residues is replaced by a semicarbazide. This substitution of a nitrogen for the α-carbon center results in conformational restrictions, which bend the peptide about the aza-amino acid residue away from a linear geometry. The resulting azapeptide turn conformations have been observed by x-ray crystallography and spectroscopy, as well as predicted based on computational models. In biologically active peptide analogs, the aza-substitution has led to enhanced activity and selectivity as well as improved properties, such as prolonged duration of action and metabolic stability. In light of these characteristics, azapeptides have found important uses as receptor ligands, enzyme inhibitors, drugs, pro-drugs, probes and imaging agents. Recent improvements in synthetic methods for their procurement have ushered in a new era of azapeptide chemistry. This review aims to provide a historical look at the development of azapeptide science along with a focus on recent developments and perspectives on the future of this useful tool for medicinal chemistry.
氮杂肽是一种肽类似物，其中一个或多个氨基酸残基被氨基脒取代。这种氮原子取代α-碳中心导致构象受限，使肽围绕氮杂氨基酸残基弯曲，偏离线性几何形状。通过 X 射线晶体学和光谱学观察到了氮杂肽的构象，也可以根据计算模型进行预测。在具有生物活性的肽类似物中，氮杂取代导致活性和选择性增强，以及改善了性质，如作用持续时间延长和代谢稳定性提高。鉴于这些特性，氮杂肽已被广泛用作受体配体、酶抑制剂、药物、前药、探针和成像剂。其采购的合成方法的最新改进开创了氮杂肽化学的新时代。本文旨在回顾氮杂肽科学的发展，并重点介绍最近的进展和对这一有用的药物化学工具的未来展望。
