Glycosamino acids: building blocks for combinatorial synthesis-implications for drug discovery.
Glycosamino acids: building blocks for combinatorial synthesis-implications for drug discovery.
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DOI：
10.1002/1521-3773(20020118)41:2
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发表时间：
2002-01
影响因子：
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通讯作者：
F. Schweizer
中科院分区：
文献类型：
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作者：
F. Schweizer
碳水化合物的独特功能，包括能量储存、运输、蛋白质功能调节、细胞间粘附、信号转导、恶性转化以及病毒和细菌细胞表面识别，是其重要的药物潜力的基础。在这一重要领域，组合碳水化合物文库的发展一直比较缓慢，而在小分子文库和生物聚合物领域，组合合成的发展却非常迅速。这在很大程度上是由于这类多功能化合物所固有的困难。然而，在过去的七年中，已经设计出了应对这些问题的策略，并且出现了组合碳水化合物库。将氨基酸片段结合到碳水化合物支架中产生糖胺酸，由于已建立的自动化肽合成，糖胺酸是制备碳水化合物库的有吸引力的构建块。衍生化以及糖胺酸的同源和异聚可以用来制造具有独特性质的新结构。糖胺酸是碳水化合物和氨基酸的杂化结构，可用于产生潜在的糖仿制品和肽仿制品。将糖胺酸掺入多肽可以将碳水化合物结合位点工程合成多肽，这也可能影响多肽的药代动力学和动力学性质。此外，糖-氨基酸杂交种提供了巨大的结构和功能多样性，这在很大程度上是未知的，需要组合策略来有效开发。本文综述了糖胺酸的研究进展，并讨论了糖胺酸在组合合成和药物发现中的应用。本文的支持信息可从WWW上的http://www.angewandte.com或作者处获得。
The unique functions of carbohydrates, including energy storage, transport, modulation of protein function, intercellular adhesion, signal transduction, malignant transformation, and viral and bacterial cell-surface recognition, underlie a significant pharmaceutical potential. The development of combinatorial carbohydrate libraries in this important arena has been slow, in contrast to the rapid development of combinatorial synthesis in the area of small-molecule libraries and biopolymers. This is largely as a result of the inherent difficulties presented by this class of polyfunctional compounds. Nevertheless, strategies to cope with these problems have been devised over the past seven years, and combinatorial carbohydrate libraries have appeared. The incorporation of an amino acid moiety into the carbohydrate scaffold generates glycosamino acids, which are attractive building blocks for the preparation of carbohydrate-based libraries because of the well-established automated peptide synthesis. Derivatization as well as homo- and heterooligomerization of glycosamino acids can be used to create novel structures with unique properties. Glycosamino acids are hybrid structures of carbohydrates and amino acids which can be utilized to generate potential glycomimetics and peptidomimetics. The incorporation of glycosamino acids into peptides allows the engineering of carbohydrate-binding sites into synthetic polypeptides, which may also influence the pharmacokinetic and dynamic properties of the peptides. Furthermore, sugar-amino acid hybrids offer a tremendous structural and functional diversity, which is largely unexplored and requires combinatorial strategies for efficient exploitation. This article provides an overview of previous work on glycosamino acids and discusses their use in combinatorial synthesis and drug discovery. Supporting information for this article is available on the WWW under http://www.angewandte.com or from the author.