Relative Helix-Helix Conformations in Branched Aromatic Oligoamide Foldamers
Relative Helix-Helix Conformations in Branched Aromatic Oligoamide Foldamers
复制标题
DOI：
10.1021/ja110677a
复制
发表时间：
2011-03-09
影响因子：
15
通讯作者：
Huc, Ivan
中科院分区：
文献类型：
--
作者：
Delsuc, Nicolas;Massip, Stephane;Huc, Ivan
从头设计和合成大型的、组织良好的、类似三级的α -肽折叠结构是困难的，因为它依赖于内在稳定性相对较弱的二级折叠基序内部和之间的多重合作相互作用。8-氨基-2-喹啉羧酸低聚酰胺的非常稳定的螺旋结构提供了一种绕过这一困难的方法，因为它们能够折叠成可预测和稳定的二级基序。设计并合成了由两对四聚体(1)、五聚体(2)或八聚体(3)低聚物通过乙二醇间隔剂连接而成的支链结构。短间隔将两个螺旋紧靠在一起，从而使它们之间能够相互作用。系统中允许的自由度是明确定义的：两个螺旋的相对P或M手性；螺旋轴的相对方向；乙烯间隔物的间扭或反构象。研究1-3在固态和溶液中的结构，可以绘制出它们的构象偏好和动力学的详细图像。固态结构的高度可变性提供了许多可能的溶液构象的快照。证明了螺旋-螺旋手性通信取决于溶剂和螺旋-螺旋界面上的一组确定的侧链。发现侧链的交错限制了乙烯间隔剂的自由旋转。一个固态结构显示出高度的对称性，为进一步设计特定侧链/侧链定向相互作用提供了坚实的基础。
The de novo design and synthesis of large and well-organized, tertiary-like, alpha-peptidic folded architectures is difficult because it relies on multiple cooperative interactions within and between secondary folded motifs of relatively weak intrinsic stability. The very stable helical structures of oligoamides of 8-amino-2-quinoline carboxylic acid offer a way to circumvent this difficulty thanks to their ability to fold into predictable and stable secondary motifs. Branched architectures comprised of, two pairs of tetrameric (1), pentameric (2), or octameric (3) oligomers connected via an ethylene glycol spacer were designed and synthesized. The short spacer holds two helices in close proximity, thus enabling interactions between them. Degrees of freedom allowed in the system are well-defined: the relative P or M handedness of the two helices; the relative orientation of the helix axes; and the gauche or anti conformation of the ethylene spacer. Investigating the structures of 1-3 in the solid state and in solution allowed a detailed picture to be drawn of their conformational preferences and dynamics. The high variability of the solid state structures provides many snapshots of possible solution conformations. Helix-helix handedness communication was evidenced and shown to depend both on solvent and on a defined set of side chains at the helix-helix interface. Interdigitation of the side chains was found to restrict free rotation about the ethylene spacer. One solid state structure shows a high level of symmetry and provides a firm basis to further design specific side chain/side chain directional interactions.