Oligosaccharides Against Enteric Infections

低聚糖对抗肠道感染

• 批准号: 7932085
• 负责人: Leila Aminova
• 金额: $ 34.04万
• 依托单位: ZUCHEM, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7932085
• 关键词: Cessation of life; Child; Collection; Dose; Enteral; Escherichia coli O157; Exposure to; In Vitro; Infant; Infection; Intestines; Methods; Monosaccharides; Nucleotides; Oligosaccharides; Phosphotransferases; Polysaccharides; Preparation; Probiotics; Production; Prophylactic treatment; Protein Engineering; Research; Specificity; Structure-Activity Relationship; System; Technology; Testing; analog; antimicrobial; antimicrobial drug; base; effective therapy; efficacy trial; gastrointestinal; glycosyltransferase; high risk; monomer; novel; nucleotidyltransferase; paragloboside; pathogen; pre-clinical; preclinical study; research clinical testing; safety study; scale up; sugar

DESCRIPTION (provided by applicant): Oligosaccharides may be an effective treatment or prophylaxis for gastrointestinal pathogeny. However, we foresee two significant barriers: little is known about the structure activity relationship between oligosaccharides and their targets, and preparation of oligosaccharides in quantities large enough for preclinical studies is a significant step in developing them for use as antimicrobial agents. Large enough quantities of oligosaccharides need to be synthesized to undergo safety studies, dose- ranging, and efficacy trials in infants and children who are at high risk of exposure to gastrointestinal pathogens. Furthermore, ready synthesis of analogs of these oligosaccharides containing modified and alternative monomers is required to study the structure activity relationship. Additionally, access to such analogs would allow for the discovery of novel antimicrobial oligos with perhaps different activity or specificity. A promising approach to synthesizing oligosaccharides and analogs in sufficient quantities for preclinical and clinical testing is using glycosyltransferases in vitro with simple starting materials such as monosaccharides or readily available polysaccharides and nucleotide activated sugars.

描述（由申请人提供）：寡聚核苷酸可能是一种有效的治疗或预防胃肠道病因的药物。然而，我们预见到两个重要的障碍：很少有人知道寡糖和它们的目标之间的结构活性关系，和制备足够大的量的寡糖临床前研究是一个重要的步骤，在开发它们作为抗菌剂。需要合成足够大量的低聚糖，以便在暴露于胃肠道病原体的高风险婴儿和儿童中进行安全性研究、剂量范围确定和疗效试验。此外，需要快速合成含有修饰和替代单体的这些寡糖的类似物以研究结构活性关系。此外，获得这样的类似物将允许发现可能具有不同活性或特异性的新型抗微生物寡核苷酸。合成足够量的寡糖和类似物用于临床前和临床测试的一种有前途的方法是在体外使用糖基转移酶，其具有简单的起始材料，例如单糖或容易获得的多糖和核苷酸活化的糖。