Studies of naturally occurring structurally modified carbohydrates

碳水化合物的结构修饰是自然界中常见的现象。例如，硫酸化 许多蛋白聚糖、糖蛋白和糖脂中存在的碳水化合物被认为发挥着作用 在特定分子识别过程中发挥重要作用。此外，唾液酸的修饰 单糖，如硫酸化、磷酸化、甲基化、乙酰化和乳酰化，导致 观察自然界中 50 多种不同形式的唾液酸。然而，人们对特区知之甚少 由于技术上的困难，这些碳水化合物的修饰（结构-活性关系） 均质结构修饰的碳水化合物和糖复合物。该计划的长期目标是 开发新的化学酶方法，用天然物质合成结构确定的碳水化合物 发生的修饰并提供对其生物学作用的更好理解。在目前的拨款中 在此期间，我们将重点研究含唾液酸的结构。 唾液酸是一类带负电荷的 9 碳糖，主要被发现为 脊椎动物复合糖的最外层碳水化合物。作为其他人遇到的前线 作为生物分子，唾液酸在多种生理和病理过程中发挥着关键作用，包括 细胞间相互作用、信号传导、炎症和感染等基于唾液酸的识别过程 据信与唾液酸的精细结构密切相关，而碳水化合物结构则与唾液酸的精细结构密切相关。 唾液酸，以及之间的连接类型。我们建议采用化学酶法合成 包含大多数这些天然存在的不同结构的唾液酸苷库并将其应用于 蛋白质-碳水化合物相互作用研究。该提案的具体目标是： 1. 化学合成 多种唾液酸类似物及其前体； 2.酶法合成CMP-唾液酸衍生物和 唾液酸苷库； 3.使用唾液酸研究获得的唾液酸苷库的构效关系（SAR） 酸识别蛋白。由于唾液酸是许多生理和病理的关键元素 过程，完成拟议的研究也可能促进新的发现和开发 治疗人类疾病，如癌症、炎症、传染病和其他致病性疾病。

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.