Department of Chemical and Biological Engineering, University of Wisconsin-Madison, 1415 Engineering Drive, Madison, Wisconsin 53706, United States.
J Am Chem Soc. 2011 Mar 23;133(11):3981-8. doi: 10.1021/ja1089183. Epub 2011 Mar 1.
Oligomers of β-amino acids ("β-peptides") can be designed to fold into stable helices that display side chains with a diverse range of chemical functionality in precise arrangements. We sought to determine whether the predictable, three-dimensional side-chain patterns generated by β-peptides could be used in combination with single-molecule force spectroscopy to quantify how changes in nanometer-scale chemical patterns affect intermolecular interactions. To this end, we synthesized β-peptides that were designed to be either globally amphiphilic (GA), i.e., display a global segregation of side chains bearing hydrophobic and cationic functional groups, or non-globally amphiphilic (iso-GA), i.e., display a more uniform distribution of hydrophobic and cationic functional groups in three-dimensions. Single-molecule force measurements of β-peptide interactions with hydrophobic surfaces through aqueous solution (triethanolamine buffer, pH 7.2) reveal that the GA and iso-GA isomers give rise to qualitatively different adhesion force histograms. The data are consistent with the display of a substantial nonpolar domain by the GA oligomer, which leads to strong hydrophobic interactions, and the absence of a comparable domain on the iso-GA oligomer. This interpretation is supported by force measurements in the presence of methanol, which is known to disrupt hydrophobic interactions. Our ability to associate changes in measured forces with changes in three-dimensional chemical nanopatterns projected from conformationally stable β-peptide helices highlights a contrast between this system and conventional peptides (α-amino acid residues): conventional peptides are more conformationally flexible, which leads to uncertainty in the three-dimensional nanoscopic chemical patterns that underlie measured forces. Overall, we conclude that β-peptide oligomers provide a versatile platform for quantifying intermolecular interactions that arise from specific functional group nanopatterns.
β-氨基酸（“β-肽”）的低聚物可以设计成折叠成稳定的螺旋，这些螺旋在精确的排列中显示出具有广泛化学功能的侧链。我们试图确定β-肽产生的可预测的、三维的侧链图案是否可以与单分子力谱结合使用，以量化纳米级化学图案的变化如何影响分子间相互作用。为此，我们合成了设计为全局两亲性（GA）的β-肽，即显示带有疏水性和阳离子官能团的侧链的全局分离，或非全局两亲性（iso-GA），即显示在三维中疏水性和阳离子官能团更均匀的分布。通过水溶液（三乙醇胺缓冲液，pH7.2）中的单分子力测量，β-肽与疏水性表面的相互作用表明，GA 和 iso-GA 异构体产生定性不同的粘附力直方图。数据与 GA 低聚物显示出实质性的非极性域一致，这导致了强烈的疏水性相互作用，而 iso-GA 低聚物则不存在可比的域。这种解释得到了在甲醇存在下的力测量的支持，甲醇已知会破坏疏水性相互作用。我们能够将测量力的变化与从构象稳定的β-肽螺旋中投射出的三维化学纳米图案的变化相关联，这突出了该系统与传统肽（α-氨基酸残基）之间的对比：传统肽更构象灵活，这导致了测量力所依据的三维纳米级化学图案的不确定性。总的来说，我们得出结论，β-肽低聚物为定量研究特定功能基团纳米图案引起的分子间相互作用提供了一个通用的平台。
