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）：寡糖可能是胃肠道病原体的有效治疗方法或预防。但是，我们预见到两个重要的障碍：对寡糖及其靶标之间的结构活动关系知之甚少，并且在足够大的临床前研究的数量中制备寡糖的寡糖是开发它们作为抗菌药物的重要一步。需要合成足够数量的寡糖来进行安全研究，剂量和疗效试验，这些婴儿和儿童处于胃肠道病原体的高风险。此外，需要研究含有改良和替代单体的这些寡糖的类似物来研究结构活性关系。此外，访问此类类似物将允许发现具有不同活性或特异性的新型抗菌寡聚。一种有前途的方法，用于临床前和临床测试的足够量中的寡糖和类似物是在体外使用糖基转移酶，例如单糖类（例如单糖）或易于使用的多糖和核苷酸活性糖。