Department of Chemistry and Chemical Biology, Indiana University-Purdue University, Indianapolis, 402 N. Blackford Street, Indianapolis, IN 46202, USA.
Molecules. 2010 Jul 20;15(7):4961-83. doi: 10.3390/molecules15074961.
Amino acids are Nature's combinatorial building blocks. When substituted on both the amino and carboxyl sides they become the basic scaffold present in all peptides and proteins. We report a solid-phase synthetic route to large combinatorial variations of this fundamental scaffold, extending the variety of substituted biomimetic molecules available to successfully implement the Distributed Drug Discovery (D3) project. In a single solid-phase sequence, compatible with basic amine substituents, three-point variation is performed at the amino acid a-carbon and the amino and carboxyl functionalities.
氨基酸是大自然的组合构建模块。当它们在氨基和羧基两侧被取代时，就成为所有肽和蛋白质中存在的基本支架。我们报告了一种固相合成途径，可以对这种基本支架进行大规模组合变化，从而扩展了可用的取代仿生分子的多样性，成功地实现了分布式药物发现（D3）项目。在一个与碱性胺取代基兼容的单一固相序列中，在氨基酸 a-碳以及氨基和羧基官能团处进行三点变化。
