Studies of naturally occurring structurally modified carbohydrates

天然结构修饰碳水化合物的研究

• 批准号: 7570060
• 负责人: Xi Chen
• 金额: $ 27.57万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7570060
• 关键词: Acetylation; Acylneuraminate Cytidylyltransferase; Anabolism; Animals; Binding; Binding Proteins; Biochemical; Biological; Biological Process; Carbohydrates; Carbon; Cell Communication; Cells; Charge; Chemicals; Cytidine Monophosphate N-Acetylneuraminic Acid; Degradation Pathway; Development; Disease; Enzymes; Epitopes; Escherichia coli; Family; Glycoconjugates; Glycolipids; Glycoproteins; Glycosaminoglycans; Goals; Grant; Hemagglutinin; Heparin; Human; Indium; Infection; Inflammation; Inflammatory; Inorganic Sulfates; Keratin; Lactams; Lactones; Lead; Libraries; Ligands; Link; Malignant Neoplasms; Mannose; Membrane Glycoproteins; Methods; Methylation; Modification; Monosaccharides; N-Acetylneuraminate lyase; Nature; Neuraminidase; Oligosaccharides; Pasteurella multocida; Pathologic Processes; Phosphorylation; Physical condensation; Physiological; Physiology; Pituitary Hormones; Play; Positioning Attribute; Process; Protein-Carbohydrate Interaction; Proteins; Proteoglycan; Pyruvate; Pyruvates; Reaction; Research; Research Personnel; Role; Selectins; Sialic Acids; Sialyltransferases; Signal Transduction; Source; Structure; Structure-Activity Relationship; Substrate Specificity; Sulfoglycosphingolipids; System; Unspecified or Sulfate Ion Sulfates; Vertebrates; Viral; Virus; analog; analytical method; base; carbohydrate structure; chemical synthesis; dermatan sulfate chondroitin sulfate; human disease; microorganism; molecular recognition; novel; novel therapeutics; pathogenic bacteria; programs; seminolipid; sugar; sulfation

Structural modification of carbohydrates is a common phenomenon in nature. For example, sulfated carbohydrates presented in a number of proteoglycans, glycoproteins, and glycolipids are believed to play important roles in specific molecular recognition processes. Furthermore, modifications of sialic acid monosaccharides, such as sulfation, phosphorylation, methylation, acetylation, and lactylation, lead to the observation of more than 50 different sialic acid forms in nature. Little is known, however, about the SAR (structure-activity relationship) of these carbohydrate modifications due to technical difficulties in obtaining homogenous structurally modified carbohydrates and glycoconjugates. The long-term goal of this program is to develop novel chemo-enzymatic methods for synthesizing structurally defined carbohydrates with naturally occurring modifications and to provide better understanding of their biological roles. In the current granting period, we will focus our efforts on the sialic acid-containing structures. Sialic acids are a family of negatively charged 9-carbon sugars that have been predominantly found as the outermost carbohydrates of vertebrate glycoconjugates. As the frontline encountered by other biomolecules, sialic acids play pivotal roles in a variety of physiological and pathological processes, including cell-cell interaction, signaling, inflammation, and infection etc. The sialic acid-based recognition processes are believed to be closely related to the fine structures of the sialic acids, the carbohydrate structures linked to the sialic acids, and the types of the linkages in between. We propose to chemo-enzymatically synthesize a sialoside library containing the majority of these naturally occurring diverse structures and apply it in protein-carbohydrate interaction studies. The specific aims of the proposal are to: 1. chemically synthesize diverse sialic acid analogs and their precursors; 2. enzymatically synthesize CMP-sialic acid derivatives and a sialoside library; 3. study structure-activity relationship (SAR) of the obtained sialoside library using sialic acid-recognizing proteins. As sialic acids are key elements in many physiological and pathological processes, accomplishing the proposed studies may also facilitate the discovery and development of new therapeutics for human diseases such as cancer, inflammatory, infectious, and other pathogenic diseases.

碳水化合物的结构修饰是自然界普遍存在的现象。例如，硫酸盐