Oligosaccharides Against Enteric Infections

描述(申请人提供)：低聚糖可能是胃肠道疾病的有效治疗或预防方法。然而，我们预见到两个重大的障碍：对低聚糖与其靶标之间的结构活性关系知之甚少，以及制备足够数量的低聚糖用于临床前研究是开发它们作为抗菌剂的重要一步。需要合成足够数量的低聚糖，以便在婴儿和儿童中进行安全性研究、剂量范围和疗效试验，这些婴儿和儿童面临着接触胃肠道病原体的高风险。此外，为了研究构效关系，需要准备好合成含有修饰和替代单体的这些寡糖的类似物。此外，获得这种类似物将有助于发现具有不同活性或特异性的新型抗菌寡核苷酸。利用体外糖基转移酶和简单的原料，如单糖或易得的多糖和核苷酸活性糖，可以合成足够数量的寡糖及其类似物，用于临床前和临床试验。

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.