Appella D H, Christianson L A, Klein D A, Powell D R, Huang X, Barchi J J, Gellman S H
Department of Chemistry, University of Wisconsin, Madison 53706, USA.
Nature. 1997 May 22;387(6631):381-4. doi: 10.1038/387381a0.
Proteins and RNA are unique among known polymers in their ability to adopt compact and well-defined folding patterns. These two biopolymers can perform complex chemical operations such as catalysis and highly selective recognition, and these functions are linked to folding in that the creation of an active site requires proper juxtaposition of reactive groups. So the development of new types of polymeric backbones with well-defined and predictable folding propensities ('foldamers') might lead to molecules with useful functions. The first step in foldamer development is to identify synthetic oligomers with specific secondary structural preferences. Whereas alpha-amino acids can adopt the well-known alpha-helical motif of proteins, it was shown recently that beta-peptides constructed from carefully chosen beta-amino acids can adopt a different, stable helical conformation defined by interwoven 14-membered-ring hydrogen bonds (a 14-helix; Fig. 1a). Here we report that beta-amino acids can also be used to design beta-peptides with a very different secondary structure, a 12-helix (Fig. 1a). This demonstrates that by altering the nature of beta-peptide residues, one can exert rational control over the secondary structure.
蛋白质和RNA在已知聚合物中独具特色，能够呈现紧密且明确的折叠模式。这两种生物聚合物可执行复杂的化学操作，如催化作用和高度选择性识别，并且这些功能与折叠相关，因为活性位点的形成需要反应基团的恰当并列。因此，开发具有明确且可预测折叠倾向的新型聚合物主链（“折叠体”）可能会产生具有实用功能的分子。折叠体开发的第一步是识别具有特定二级结构偏好的合成寡聚物。虽然α-氨基酸可以呈现蛋白质中众所周知的α-螺旋基序，但最近研究表明，由精心挑选的β-氨基酸构建的β-肽可以呈现由交织的14元环氢键定义的不同的稳定螺旋构象（14-螺旋；图1a）。在此，我们报告β-氨基酸还可用于设计具有截然不同二级结构——12-螺旋（图1a）的β-肽。这表明通过改变β-肽残基的性质，能够对二级结构进行合理控制。
