Aromatic Interactions in Nucleotide/Carbohydrate Binding

核苷酸/碳水化合物结合中的芳香族相互作用

• 批准号: 6854888
• 负责人: MARCEY L WATERS
• 金额: $ 25.86万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-05 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6854888
• 关键词: DNA; binding sites; carbohydrate receptor; carbohydrates; carbopolycyclic compound; fluoresceins; high performance liquid chromatography; intermolecular interaction; mass spectrometry; nuclear magnetic resonance spectroscopy; nucleotides; protein binding; protein folding; protein structure

Molecular design is a powerful tool for assessing our knowledge of molecular recognition events and noncovalent interactions. Our current knowledge of molecular recognition has been advanced greatly through the design of molecular receptors, from early work on crown ethers to current work on receptors for anions. Much has been learned about the complex aspects of protein folding and structure through the de novo design of proteins as well. Conceptually, protein de novo design is also a powerful method for defining critical elements in biomolecular recognition. In this proposal we aim to utilize a designed structured peptide to investigate aspects of biomolecular recognition, including protein-nucleic acid and protein-carbohydrate recognition. We have developed a beta-hairpin peptide that binds to nucleotides and ssDNA through a combination of aromatic stacking and electrostatic interactions. We intend to utilize this system to investigate aspects of sequence and structure-selective recognition of DNA. With regard to structure selective recognition, we will investigate the role of stacking interactions in selective recognition of alkylated bases in duplex DNA, mimicking glycosylase enzymes and mRNA-cap binding proteins. These studies have potential applications to chemotherapy, control of gene expression, and antiviral therapies. A beta-hairpin system will also be utilized to study the carbohydrate-pi interaction, which is a poorly understood molecular recognition motif that is commonly found in carbohydrate binding proteins. We will compare the findings of these studies to those of cation-pi, pi-pi, and hydrophobic interactions to determine fundamental aspects of this type of interaction. We will then apply it to the development of carbohydrate receptors as mimics of carbohydrate-binding proteins. These studies will provide important insights into protein binding of carbohydrates, which is a crucial aspect of biomolecular recognition.

分子设计是评估我们对分子识别事件和非共价相互作用知识的有力工具。通过分子受体的设计，我们目前对分子识别的知识有了很大的进步，从早期的冠醚工作到现在的阴离子受体工作。关于蛋白质折叠和结构的复杂方面，人们也通过蛋白质的从头设计学到了很多。从概念上讲，蛋白质从头设计也是确定生物分子识别中关键元素的一种有效方法。在这项提案中，我们的目标是利用设计的结构肽来研究生物分子识别的各个方面，包括蛋白质-核酸和蛋白质-碳水化合物。 承认。我们已经开发出一种β-发夹多肽，它通过芳香堆积和静电相互作用结合到核苷酸和单链DNA上。我们打算利用这个系统来研究DNA的序列和结构选择性识别的各个方面。在结构选择性识别方面，我们将研究堆积相互作用在模拟糖基酶和mRNA帽结合蛋白的双链DNA中烷基化碱基选择性识别中的作用。这些研究在化疗、基因表达控制和抗病毒治疗方面具有潜在的应用价值。还将利用β-发夹系统来研究碳水化合物-圆周率的相互作用，这是一个鲜为人知的分子识别基序，通常在碳水化合物结合蛋白中发现。我们将把这些研究的结果与阳离子-pi、pi-pi和疏水相互作用的结果进行比较，以确定这类相互作用的基本方面。然后，我们将把它应用于碳水化合物受体的开发，作为碳水化合物结合蛋白的模拟物。这些研究将为 碳水化合物的蛋白质结合，这是生物分子识别的一个关键方面。