Evidence for a 3(10)-helical conformation of an eight-residue peptide from 1H-1H rotating frame Overhauser studies.
Evidence for a 3(10)-helical conformation of an eight-residue peptide from 1H-1H rotating frame Overhauser studies.
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来自 1H-1H 旋转框架 Overhauser 研究的八残基肽的 3(10) 螺旋构象的证据。
DOI：
10.1002/bip.360330615
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发表时间：
1993
期刊：
影响因子：
2.9
通讯作者：
Kuki,A
中科院分区：
文献类型：
--
作者：
Basu,G;Kuki,A
大量最近的实验研究表明，其序列取自几个设计基序之一的合成肽实际上可以在溶液中获得大量的螺旋含量。这些关键研究已经开始建立导致高稳定性的有限长度螺旋的序列类别，并提供了基于多螺旋的合成蛋白质从头设计所需的基本信息。通过离子氨基酸的盐桥配对、4通过利用螺旋大偶极的静电场以及通过加入受欢迎的螺旋终止残基，可以实现螺旋的成功稳定。虽然普遍的特征仍然是使用由具有高内在螺旋偏好的常见氨基酸主导的序列，如丙氨酸或亮氨酸，但二烷基氨基酸a-氨基异丁酸(AIB)在赋予长度为8-10的短合成肽高度螺旋性方面是相当独特的，是大多数其他序列所需长度的一半。这种富含AIB的设计还可以构建疏水螺旋。由于a，a-二甲基团在C“周围产生一种独特的和有充分证据的空间应变，主链扭转角的构象空间(4，4)被严格限制在所需的螺旋区域。然而，这个狭窄的螺旋构象空间跨越了两种螺旋，a-螺旋和310-螺旋。根据长度、组成和精确序列等关键因素，11，12富含AIB的多肽可能采用任何一种螺旋构象，有时可能产生对称性较低的混合螺旋构象，正如在晶相中所证明的那样。13不幸的是，可用的解决方案结构不那么精确，也没有提供如此详细的图片。AIB多肽的典型一维(1D)‘H-NMR实验计算了多肽中分子内酰胺氢键的数量，从而推断出310氢键或氢键方案。虽然有用，但这种技术不能区分具有相同氢键总数的不同结构，因此不能提供关于肽的三维结构的直接信息。
Numerous recent experimental studies have shown that synthetic peptides whose sequences are drawn from one of several design motifs can in fact achieve substantial helical content in solution.'4 These pivotal studies have begun to establish the sequence classes that lead to finite length helices of high stability, and provide in addition fundamental information required for the de novo design of synthetic proteins based on multihelix Successful stabilization of helices can be achieved by salt bridge pairing of ionic amino acids, 4 by exploiting the electrostatic field of the helix macrodipole,'and by incorporation of favored helix terminating residues? While a universal characteristic remains the use of sequences dominated by the common amino acids with high intrinsic helical preference, such as alanine or leucine, the di-aalkylated amino acid a-aminoisobutyric acid (Aib) is rather unique in conferring high helicity onto short synthetic peptides of length 8-10, half the length required of most other sequences. This Aib-rich design also enables the construction of hydrophobic helices. Since the a, a-dimethyl group produces a distinctive and well-documented steric strain around C", the conformational space (4, 4) of backbone torsional angles is severely restricted to the desired helical region." Nevertheless, this narrow helical conformational space spans two kinds of helices, the a-helix and the 310-helix. Depending on critical factors such as the length, composition, and exact sequence, 11, 12 the Aib rich peptide may adopt a helical geometry of either kind, and on occasion hybrid helical conformations with lower symmetry may result, as has been demonstrated in the crystalline phase. 13Unfortunately, available solution structures are less precise and have not provided such detailed pictures. A typical one-dimensional (1D)'H-nmr experiment for an Aib peptide counts the number of intramolecular amide hydrogen bonds in the peptide and thereby infers either a 310 H-bonding scheme or an a H-bonding scheme. While useful, this technique cannot distinguish between different structures with the same total number of H bonds, and therefore provides no direct information about the threedimensional structure of the peptide.