Raguse Tami L, Lai Jonathan R, Gellman Samuel H
Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
J Am Chem Soc. 2003 May 14;125(19):5592-3. doi: 10.1021/ja0341485.
We report a significant and unanticipated advance in the study of beta-amino acid-based foldamers: a small proportion of highly preorganized residues can impart high stability to a specific helical secondary structure in water. Most of the residues in these beta-peptides (2 and 3) are intrinsically flexible. Flexible beta-amino acids can be readily and enantiospecifically prepared in functionally diverse forms, but preorganized residues with side chains are rare and challenging to synthesize. Our findings demonstrate that interspersing a few copies of an unfunctionalized but rigid residue among a larger number of flexible residues with diverse side chains is a viable strategy for creating beta-peptides that adopt the 14-helix conformation and therefore display side chains in a predictable spatial arrangement. These results are significant because they enhance the prospects of developing beta-peptides with useful activities.
我们报告了基于β-氨基酸的折叠体研究中一项重大且出人意料的进展：一小部分高度预组织化的残基能够赋予特定螺旋二级结构在水中高度的稳定性。这些β-肽（2和3）中的大多数残基本质上是柔性的。柔性β-氨基酸能够以功能多样的形式轻松且对映体特异性地制备，但带有侧链的预组织化残基很少见且合成具有挑战性。我们的研究结果表明，在大量具有不同侧链的柔性残基中穿插几个无功能但刚性的残基是一种可行的策略，用于创建采用14-螺旋构象并因此以可预测的空间排列展示侧链的β-肽。这些结果意义重大，因为它们增强了开发具有有用活性的β-肽的前景。
