Calvin College, Chemistry and Biochemistry, Grand Rapids, Michigan, USA.
J Pept Sci. 2013 May;19(5):277-82. doi: 10.1002/psc.2496. Epub 2013 Mar 2.
Stable peptides have been explored as epitope mimics for protein-protein and protein-nucleic acid interactions; however, presentation of a regular structure is critical. Aromatic interactions are ubiquitous and are competent at stabilizing a β-hairpin fold. The greatest stabilization has been reported from pairs of tryptophan side chains. Naphthylalanine residues are often used as tryptophan replacements, but it is not clear if 1-naphthylalanine or 2-naphthylalanine is adequate at replicating the geometry and stability observed with tryptophan aromatic interactions. Herein, a 12-residue peptide has been constructed with laterally disposed aromatic amino acids. A direct comparison is made between tryptophan and other bicyclic, unnatural amino acids. Significant stabilization is gained from all bicyclic amino acids; however, geometric analysis shows that only 1-naphthylalanine adopts a similar edge to face geometry as tryptophan, whereas the 2-naphthylalanine appears most similar to a substituted phenylalanine.
稳定肽已被探索作为蛋白质-蛋白质和蛋白质-核酸相互作用的表位模拟物；然而，呈现规则结构是至关重要的。芳香相互作用无处不在，能够稳定β发夹折叠。报道的最大稳定性来自于一对色氨酸侧链。萘基丙氨酸残基通常被用作色氨酸的替代品，但尚不清楚 1-萘基丙氨酸或 2-萘基丙氨酸是否足以复制色氨酸芳香相互作用所观察到的几何形状和稳定性。在此，构建了一个具有侧向芳香氨基酸的 12 残基肽。在色氨酸和其他双环、非天然氨基酸之间进行了直接比较。所有双环氨基酸都获得了显著的稳定性；然而，几何分析表明，只有 1-萘基丙氨酸采用与色氨酸类似的边面对称几何形状，而 2-萘基丙氨酸似乎与取代的苯丙氨酸最为相似。
