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Three-Dimensional Organization of Helices:Design Principles for Nucleobase-Functionalized beta-Peptides

机译:螺旋的三维组织:核碱基功能化β肽的设计原理

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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 |3-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 functionaliza-tion 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 14-helix in regard to double-strand recognition was tuned by the sequential order of polar beta-amino acids or by the amount of 2-aminocyclohexanecar-boxylic acid units incorporated,which are known to facilitate 14-helix formation,respectively.
机译:各种三维仿生结构的构建和分子识别是基于可预测的人工分子从头设计。在这方面,| 3-肽尤为有趣,因为已经以短序列获得了稳定的二级结构;其中一个是14个螺旋中的每三个残基具有相同的方向。每三个14螺旋侧链与核碱基的共价官能化用于基于核碱基配对的两个螺旋的可逆组织。合成了各种核碱基序列并研究了双链形成的稳定性。少至四个核碱基足以实现相当大的双链体稳定性。通过温度依赖性紫外光谱检查碱基配对的稳定性,并确认了14螺旋的形成圆二色性(CD)光谱。互补核碱基修饰的β-研究了肽螺旋的螺旋结构以及螺旋含量对双链体稳定性的影响。通过双极性β-氨基酸的顺序或通过调节2-螺旋的数量来调节14螺旋双链识别的预组织并入的氨基环己烷羧酸分子单元分别已知可促进14螺旋的形成。

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