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: 7184319
• 负责人: MARCEY L WATERS
• 金额: $ 24.52万
• 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/7184319
• 关键词: Affinity; Anions; Antiviral Therapy; Binding; Carbohydrates; Cations; Cleaved cell; Complex; Crown Ethers; DNA; DNA Damage; Development; Electrostatics; Enzymes; Event; Excision; Gene Expression; Hydrogen Bonding; Hydrophobic Interactions; Indium; Investigation; Knowledge; Learning; Methods; Molecular; Nature; Nucleic Acids; Nucleotides; Oligonucleotides; Pattern; Peptides; Proteins; RNA Cap-Binding Proteins; Rate; Role; Specificity; Structure; System; Work; base; carbohydrate binding protein; carbohydrate receptor; chemotherapy; design; dimer; insight; molecular recognition; peptide structure; protein folding; receptor; repair enzyme; tool

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的了解的强大工具。我们目前对分子识别的知识已经通过设计分子受体的设计，从冠状醚的早期工作到当前在阴离子受体上的工作。通过蛋白质的从头设计，关于蛋白质折叠和结构的复杂方面已经了解了很多。从概念上讲，从头设计也是定义生物分子识别中关键元素的强大方法。在此提案中，我们旨在利用设计的结构化肽来研究生物分子识别方面，包括蛋白质核酸和蛋白质 - 碳水化合物 认出。我们已经开发了一种β发蛋白肽，该肽通过芳族堆叠和静电相互作用的结合与核苷酸和ssDNA结合。我们打算利用该系统来研究序列和结构选择性识别DNA的方面。关于结构选择性识别，我们将研究堆叠相互作用在双链DNA中烷基化碱的选择性识别，模仿糖基化酶酶和mRNA-CAP结合蛋白中的作用。这些研究在化学疗法，基因表达和抗病毒疗法方面具有潜在的应用。 β发行系统还将用于研究碳水化合物-PI的相互作用，这是一个知识熟悉的分子识别基序，通常在碳水化合物结合蛋白中发现。我们将将这些研究的发现与阳离子PI，PI-PI和疏水相互作用的发现进行比较，以确定这种相互作用的基本方面。然后，我们将其应用于碳水化合物受体的发展，作为模仿碳水化合物结合蛋白的模仿。这些研究将为您提供重要的见解 碳水化合物的蛋白质结合，这是生物分子识别的关键方面。