Three-dimensional organization of helices:: Design principles for nucleobase-functionalized β-peptides
Three-dimensional organization of helices:: Design principles for nucleobase-functionalized β-peptides
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DOI：
10.1002/chem.200500004
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发表时间：
2005-05-20
影响因子：
4.3
通讯作者：
Diederichsen, U
中科院分区：
文献类型：
--
作者：
Chakraborty, P;Diederichsen, U
各种三维仿生结构的构建和分子识别是基于人工分子的可预测从头设计。在这方面，P-肽特别有趣，因为已经获得了具有短序列的稳定的二级结构；其中之一是14-螺旋，其中每三个残基具有相同的取向。在碱基配对的基础上，每隔3个14-螺旋侧链与碱基共价官能化，用于两个螺旋的可逆组织。合成了一系列具有不同碱基序列的β-多肽，并考察了其双链形成的稳定性。只要四个碱基就足以保证相当大的双链稳定性。用依赖温度的紫外光谱考察了碱基配对的稳定性，用圆二色谱(CD)证实了14-螺旋的形成。研究了互补碱基修饰的β-肽螺旋的择优取向以及螺旋含量对双链稳定性的影响。关于双链识别的1.4-螺旋的预组织是通过极性P-氨基酸的顺序或2-氨基环己烷羧酸单元的掺入量来调节的，这两个单元分别被认为有助于14-螺旋的形成。
The construction and molecular recognition of various three-dimensional biomimetic structures is based on the predictable de novo design of artificial molecules. In this regard P-peptides are especially interesting, since stable secondary structures are obtained already with short sequences; one of them is the 14-helix in which every third residue has the same orientation. The covalent functionalization of every third 14-helix side chain with nucleobases was used for a reversible organization of two helices based on nucleobase pairing. A series of beta-peptides with various nucleobase sequences was synthesized and the stability of double strand formation was investigated. As few as four nucleobases are sufficient for considerable duplex stability. The stability of base pairing was examined by temperature-dependent UV spectroscopy and the formation of the 14-helix was confirmed by circular dichroism (CD) spectroscopy. The preferred strand orientation of complementary-nucleobase-modified beta-peptide helices was investigated as well as the influence of helix content on the duplex stability. The preorganization of a 1.4-helix in regard to double-strand recognition was tuned by the sequential order of polar P-amino acids or by the amount of 2-aminocyclohexanecarboxylic acid units incorporated, which are known to facilitate 14-helix formation, respectively.