Department of Biotechnology and Bioscience, University of Milano Bicocca, Piazza della Scienza, 2, 20126 Milano, Italy.
J Biotechnol. 2009 Nov;144(3):234-41. doi: 10.1016/j.jbiotec.2009.05.014. Epub 2009 Jun 17.
Small molecules altering protein functions as inhibitors, agonists or antagonists, find application in systems biology enabling an analysis of the in vivo consequences of these alterations. In this context carbohydrates are ideal tools, not only because they are involved in a variety of recognition phenomena of biological relevance, but also because they are ideal scaffolds to generate libraries of bioactive compounds. Examples of design, synthesis and biological assays of different carbohydrate based inhibitors or protein ligands are reported. Exploiting NMR methods, the binding between a small molecules (inhibitor or ligand) and a protein can be detected, the affinity measured, and the interaction topology defined. This set of information is useful not only to clarify the mechanism of protein-ligand interaction, but also to improve the design of new inhibitors/ligands. The multifunctionality and the conformational rigidity of carbohydrates make this class of compounds the ideal scaffolds to generate libraries exploiting the combinatorial approach. An example of solid phase combinatorial synthesis of a library of 37 compounds is reported.
小分子通过改变蛋白质的功能，如抑制剂、激动剂或拮抗剂，在系统生物学中得到了应用，使人们能够分析这些改变的体内后果。在这方面，碳水化合物是理想的工具，不仅因为它们参与了各种具有生物学意义的识别现象，还因为它们是生成生物活性化合物文库的理想支架。本文报道了不同基于碳水化合物的抑制剂或蛋白质配体的设计、合成和生物学测定的例子。利用 NMR 方法，可以检测小分子（抑制剂或配体）与蛋白质之间的结合，测量亲和力，并确定相互作用的拓扑结构。这组信息不仅有助于阐明蛋白质-配体相互作用的机制，而且有助于改进新抑制剂/配体的设计。碳水化合物的多功能性和构象刚性使其成为利用组合方法生成文库的理想支架。本文报道了一个利用固相组合合成法合成 37 种化合物文库的例子。
