Lee Byoung-Chul, Zuckermann Ronald N, Dill Ken A
Graduate Group in Biophysics and Department of Pharmaceutical Chemistry, University of California, 600 16th Street, San Francisco, CA 94143, USA.
J Am Chem Soc. 2005 Aug 10;127(31):10999-1009. doi: 10.1021/ja0514904.
The only molecules that are currently known to fold into unique three-dimensional conformations and perform sophisticated functions are biological polymers - proteins and some RNA molecules. Our aim is to create a nonbiological sequence-specific polymer that folds in aqueous solution. Toward that end, we synthesized sequence-specific 30mer, 45mer, and 60mer peptoid oligomers (N-substituted glycine polymers) consisting of 15mer units we chained together by disulfide and oxime linkages to mimic the helical bundle structures commonly found in proteins. Because these 15mer sequences were previously shown to form defined helical structures that aggregate together at submillimolar concentrations, we expected that by covalently linking multiple 15mers together, they might fold as helical bundles. To probe whether they folded, we used fluorescence resonance energy transfer (FRET) reporter groups. We found that certain constructs fold up with a hydrophobic core and have cooperative folding transitions. Such molecules may ultimately provide a platform for designing specific functions resembling those of proteins.
目前已知唯一能折叠成独特三维构象并执行复杂功能的分子是生物聚合物——蛋白质和一些RNA分子。我们的目标是创造一种能在水溶液中折叠的非生物序列特异性聚合物。为此，我们合成了由15聚体单元组成的序列特异性30聚体、45聚体和60聚体类肽寡聚物（N-取代甘氨酸聚合物），我们通过二硫键和肟键将它们连接在一起，以模拟蛋白质中常见的螺旋束结构。由于这些15聚体序列先前已被证明能形成特定的螺旋结构，并在亚毫摩尔浓度下聚集在一起，我们预计通过将多个15聚体共价连接在一起，它们可能会折叠成螺旋束。为了探究它们是否折叠，我们使用了荧光共振能量转移（FRET）报告基团。我们发现某些构建体以疏水核心折叠，并具有协同折叠转变。这类分子最终可能为设计类似于蛋白质的特定功能提供一个平台。
