De Novo Synthesis for MedChem on Sugars

MedChem 对糖的从头合成

基本信息

批准号：
7914474
负责人：
GEORGE A O'DOHERTY
金额：
$ 0.33万
依托单位：
WEST VIRGINIA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-15 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7914474
关键词：
Address Affect Aminoglycoside Antibiotics Anti-Bacterial Agents Antibiotics Antineoplastic Agents Belief Binding Biological Biological Factors Carbohydrates Cardiac Glycosides Chemistry Communicable Diseases Complex Coupled Deoxy Sugars Development Digitoxigenin Digitoxin Disease Enzymes Goals Isomerism Laboratories Libraries Macrolides Malignant Neoplasms Methodology Methods Monosaccharides Multi-Drug Resistance Mutation National Research Service Awards Nature Oligosaccharides Outcomes Research Palladium Pharmaceutical Chemistry Pharmaceutical Preparations Pharmacologic Substance Play Positioning Attribute Reaction Research Research Design Role Scheme Solubility Structure Structure-Activity Relationship Therapeutic Agents Tissues Transmembrane Transport Universities West Virginia Work analog anticancer activity antimicrobial antitumor agent bacterial resistance base cancer therapy carbohydrate structure cost drug discovery drug resistant bacteria empowered functional group glycosylation glycosyltransferase human disease improved landomycin A new technology novel novel strategies novel therapeutics programs resistant strain sugar

项目摘要

Proposed herein is the development of new chemistry for the de novo synthesis of carbohydrates and the use of this new methodology for the synthesis of new bioactive molecules. These new bioactive structures may have activities against a range of diseases. This proposal is focus on anticancer and antibacterial compounds. The approach toward cancer is to use this new methodology to preform novel SAR studies on the carbohydrate portion of known natural products with anticancer activity. This approach will be conducted on the carbohydrate portions of digitoxin, SL0101 and Landomycin A. With regard to antibacterial agents this proposal is focused on addressing the problem of bacterial resistance. The major objectives of this proposal are to develop a concise methodology toward unnatural sugars, to develop a method for the assembly of unnatural sugars into unnatural oligosaccharides and to incorporate these unnatural sugars into carbohydrate based antibiotics, etc. Having unnatural sugar analogues of these antibiotics/antitumor agents would greatly aid in revealing which functional groups are important to these molecular interactions and in turn help prepared new more potent drugs.

本文提出的是开发从头综合的新化学碳水化合物和这种新方法用于合成新生物活性的分子。这些新的生物活性结构可能有一系列活动疾病。该提案的重点是抗癌和抗菌化合物。这癌症的方法是使用这种新方法来预成新颖的SAR研究在具有抗癌活性的已知天然产物的碳水化合物部分上。这方法将在digitoxin，sl0101和 Landomycin A.关于抗菌剂，该提案的重点是解决细菌抗性的问题。该提案的主要目的是开发一种简洁的方法论朝着不自然的糖开发出一种将不自然糖组装到中的方法非天然的寡糖，并将这些不自然的糖掺入碳水化合物中基于这些抗生素/抗生素的不自然糖类似物的抗生素等代理将极大地帮助揭示哪些官能团对这些官能团体很重要分子相互作用，进而有助于制备新的更有效的药物。