Laboratory for Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, 9000, Ghent, Belgium.
Amino Acids. 2013 Oct;45(4):613-89. doi: 10.1007/s00726-013-1521-1. Epub 2013 Aug 18.
This compendium focuses on functionalised sugar amino acids (SAAs) and their 3- to 6-membered nitrogen heterocyclic and carbocyclic analogues. The main benefit of using SAAs and their related nitrogen and carbon congeners in the production of peptidomimetics and glycomimetics is that their properties can be readily altered via modification of their ring size, chemical manipulation of their numerous functional groups and fine-tuning of the stereochemical arrangement of their ring substituents. These building blocks provide access to hydrophilic and hydrophobic peptide isosteres whose physical properties allow entry to a region of chemotherapeutic space which is still under-explored by medicinal chemists. These building blocks are also important in providing amino acids whose inherent conformational bias leads to predisposition to secondary structure upon oligomerisation in relatively short sequences. These foldamers, particularly those containing ω-amino acids, provide an additional opportunity to expand access to the control of structures by artificial peptides. The synthesis and biological evaluation of these building blocks in glycomimetics and peptidomimetics systems keep expanding the reach of the glycosciences to the medical sciences, provide a greater outlook onto the wide range of cellular functions of saccharides and their derivatives involved and greater insight into the nature of oligosaccharide and protein folding.
本纲要重点介绍功能化糖氨基酸（SAAs）及其 3-6 元氮杂环和碳环类似物。在肽模拟物和糖模拟物的生产中使用 SAA 及其相关的氮和碳同系物的主要好处是，通过改变其环大小、对其众多功能基团进行化学修饰以及微调其环取代基的立体化学排列，可以轻松改变它们的性质。这些构建块可用于亲水性和疏水性肽类似物，其物理性质允许进入化学治疗空间的一个仍未被药物化学家充分探索的区域。这些构建块在提供氨基酸方面也很重要，这些氨基酸的固有构象偏向导致在相对较短的序列中寡聚化时倾向于二级结构。这些折叠体，特别是那些含有ω-氨基酸的折叠体，为通过人工肽进一步控制结构提供了机会。在糖模拟物和肽模拟物系统中这些构建块的合成和生物学评估不断扩展糖科学在医学科学中的应用范围，更广泛地了解涉及的糖及其衍生物的多种细胞功能，并更深入地了解寡糖和蛋白质折叠的性质。
