SIDE CHAIN INTERACTIONS GOVERNING A-HELIX STABILITY

我们的目标是检测和测量涉及方的特定交互 影响孤立α-螺旋在水中稳定性的链 解决方案。相互作用可以是两种类型：(1)相互作用 相邻残基，以及(2)带电残基与 阿尔法螺旋偶极子。作为起点，C-肽(残基1-13) 已知核糖核酸酶A在0℃，pH为5的条件下形成30%的螺旋， 鉴于Zimm-Bragg方程和主客体数据预测NO 13-残基多肽可以在水中显示可测量的α-螺旋形成， 无论氨基酸序列或温度。因此，特定的 侧链相互作用对于C-肽螺旋的稳定性必须是重要的。 我们的方法是使用化学合成的C肽类似物。我们 发现两个带电的基团，Glu2-和His12+，在分子的两端 螺旋在稳定C-肽螺旋方面起着关键作用。我们有 还发现Glu9可以在不损失螺旋稳定性的情况下被取代，以及 因此，一个可能的Glu9-His 12+盐桥并不重要.我们 将使用相同的方法测试Glu2-Arg10+盐桥。测试 正在检测可能的稳定螺旋的相互作用，包括 Glu2-、His12+和Alpha-螺旋偶极。我们还将测试 成对的特定侧链之间的邻居依赖相互作用 残留物。

Our aim is to detect and measure specific interactions involving side chains that affect the stability of an isolated Alpha-helix in aqueous solution. The interactions can be of two types: (1) interactions between neighboring residues, and (2) interactions between charged residues and the Alpha-helix dipole. As a starting point, the C-peptide (residues 1-13) of ribonuclease A is known to show 30% helix formation at 0 degrees C, pH 5, whereas the Zimm-Bragg equation and host-guest data predict that no 13-residue peptide can show measurable Alpha-helix formation in water, regardless of amino acid sequence or temperature. Consequently, specific side chain interactions must be important for C-peptide helix stability. Our approach is to use chemically synthesized analogs of C-peptide. We have found that two charged groups, Glu2- and His12+, at either end of the helix play a critical role in stabilizing the C-peptide helix. We have also found that Glu9 can be replaced without loss of helix stability, and therefore that a possible Glu9-...His12+ salt bridge is not important. We will use the same approach to test for a Glu2-...Arg10+ salt bridge. Tests are in progress to detect possible helix-stabilizing interactions involving Glu2-, His12+ and the Alpha-helix dipole. We will also test for neighbor-dependent interactions between side chains in pairs of specific residues.