Huang Kai, Wu Cindy W, Sanborn Tracy J, Patch James A, Kirshenbaum Kent, Zuckermann Ronald N, Barron Annelise E, Radhakrishnan Ishwar
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA.
J Am Chem Soc. 2006 Feb 8;128(5):1733-8. doi: 10.1021/ja0574318.
Non-natural polymers with well-defined three-dimensional folds offer considerable potential for engineering novel functions that are outside the scope of biological polymers. Here we describe a family of N-substituted glycine or "peptoid" nonamers that folds into an unusual "threaded loop" structure of exceptional thermal stability and conformational homogeneity in acetonitrile. The structure is chain-length-specific and relies on bulky, chiral side chains and chain-terminating functional groups for stability. Notable elements of the structure include the engagement of the positively charged amino terminus by carbonyl groups of the backbone through hydrogen bonding interactions and shielding of polar groups from and near-complete exposure of hydrophobic groups to solvent, in a manner resembling a folded polypeptide globular domain turned inside-out. The structure is stable in a variety of organic solvents but is readily denatured in any solvent/cosolvent milieu with hydrogen bonding potential. The structure could serve as a scaffold for the elaboration of novel functions and could be used to test methodologies for predicting solvent-dependent polymer folding.
具有明确三维折叠结构的非天然聚合物为设计生物聚合物范围之外的新功能提供了巨大潜力。在此，我们描述了一类N-取代甘氨酸或“类肽”九聚体，它们在乙腈中折叠成一种异常的“穿线环”结构，具有出色的热稳定性和构象均一性。该结构具有链长特异性，并且依靠庞大的手性侧链和链端官能团来维持稳定性。该结构的显著特征包括：带正电荷的氨基末端通过氢键相互作用与主链的羰基结合，极性基团被屏蔽，疏水基团几乎完全暴露于溶剂中，其方式类似于翻转 inside-out 的折叠多肽球状结构域。该结构在多种有机溶剂中稳定，但在任何具有氢键形成潜力的溶剂/共溶剂环境中都容易变性。该结构可作为构建新功能的支架，并可用于测试预测溶剂依赖性聚合物折叠的方法。
