Pérez-Payá E, Forood B, Houghten R A, Blondelle S E
Torrey Pines Institute for Molecular Studies, San Diego, California 92121, USA.
J Mol Recognit. 1996 Sep-Dec;9(5-6):488-93. doi: 10.1002/(sici)1099-1352(199634/12)9:5/6<488::aid-jmr289>3.0.co;2-f.
A study was initiated into the formation and stability of highly soluble beta-sheet macrostructures. Such beta-sheet macrostructures are useful model systems for the study of the biological function of the hydrophobic core of proteins and for the de novo design of novel catalytic mimics. In the current study, a 16-mer-alanine-based peptide (Ac-KA14K-NH2) that is highly water soluble and adopts an extremely stable macromolecular beta-sheet structure was synthesized. A tyrosine-containing analog (Ac-KYA13K-NH1) was used to study the tertiary structure of the complex by circular dichroism spectroscopy, while the influence of the charges on the complex formation and binding affinity was evaluated using a zwitterionic analog (Ac-KEA13KE-NH1). Both the secondary and tertiary structures of the beta-sheet complex were stable to denaturants, as demonstrated by far- and near-ultraviolet circular dichroism spectroscopy. Binding studies with mononucleotides have shown that the beta-sheet complex binds to molecules through both hydrophobic and electrostatic interactions. These intrinsic properties were found to be a prerequisite for the observed enhanced cleavage of phosphodiester bonds.
开展了一项关于高溶解性β-折叠宏观结构的形成与稳定性的研究。此类β-折叠宏观结构是用于研究蛋白质疏水核心的生物学功能以及从头设计新型催化模拟物的有用模型系统。在当前研究中，合成了一种高度水溶性且具有极其稳定的大分子β-折叠结构的基于16聚体丙氨酸的肽（Ac-KA14K-NH2）。使用含酪氨酸的类似物（Ac-KYA13K-NH1）通过圆二色光谱研究复合物的三级结构，同时使用两性离子类似物（Ac-KEA13KE-NH1）评估电荷对复合物形成和结合亲和力的影响。远紫外和近紫外圆二色光谱表明，β-折叠复合物的二级和三级结构对变性剂均稳定。与单核苷酸的结合研究表明，β-折叠复合物通过疏水和静电相互作用与分子结合。发现这些内在特性是观察到的磷酸二酯键增强裂解的先决条件。
