Glycolipid Immunostimulants, A symposium at the American Chemical Soc. meeting, Boston 2015

糖脂免疫刺激剂，美国化学学会研讨会。

• 批准号: 1515214
• 负责人: Richard Franck
• 金额: $ 0.5万
• 依托单位: CUNY Hunter College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2017-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1515214&HistoricalAwards=false
• 关键词: Glycolipid; Immunostimulants; symposium; American; Chemical

"Glycolipid Immunostimulants" is a symposium to be held at the Boston 2015 National Meeting of the American Chemical Society. The founding discovery leading to the titled symposium occurred 20 years ago when scientists isolated a small family of galactosylceramides (Galcers)from an Okinawan sponge. Surprisingly, Galcers stimulate mammalian immune systems. The short-term objective of the 2015 symposium is for the 100-150 participants to exchange ideas about the design and synthesis of the ideal glycolipid immunostimulant (probably a Galcer variant). The longer-term goal is to achieve a more detailed understanding of the chemistry of this significant life process. The lecture/discussion format will bring together a majority of the chemists who have synthesized the dozens of the small molecule glycolipid ligands inspired by the sponge material. There are 14 lectures planned for the one-day session. Each lecture is followed by a discussion period. This is the first-ever major symposium where the focal point is design and synthesis of ligands that are crucial for the glycolipid-based immune pathway. This symposium will foster the intellectual exchanges that will likely induce progress toward enhancing the availability of ligands for exquisite control of the immune system. The open exchange of ideas among an international group of chemists who will then interact with immunologists is also a benefit. The idea exchange will reinforce the American science ideal. Free, open and unfettered research is the way forward for science to benefit society.Since the initial observations of the immunostimulatory effect of the sponge glycolipids, their fascinating molecular biology has been elucidated. The glycolipid acts as a "linchpin" which connects a receptor on the surface of antigen-presenting cells (APC) to a receptor on natural killer T cells (NKT). When the ternary complex of APC-glycolipid-NKT is formed, a burst of cytokines ensues which signals for the ultimate immune defense. For the first dozen years of work by synthetic chemists to design and synthesize analogs of the parent sponge Galcer, the research plan was largely empirical. The structural features of the interaction of the ligand with the 2 protein receptors had not been defined. In 2007, the X-ray structure of the ternary complex was finally reported. Thus, it has become possible for chemists to incorporate the observed H-bonding and van der Waals repulsions within the complex as part of the design of newer ligands. The ultimate goal is to have ligands that favor the induction of one cytokine. At this writing, it is not yet understood as to which of the observed bonding and/or repulsion effects are determinative for which cytokine. A planned outcome of the symposium discussions is a better understanding of these details.

“糖脂免疫刺激剂”将在2015年美国化学学会波士顿全国会议上召开。20年前，科学家们从冲绳的一块海绵中分离出了半乳糖神经酰胺（Galcers）的一个小家族，这一发现奠定了这次研讨会的基础。令人惊讶的是，galgals刺激哺乳动物的免疫系统。2015年研讨会的短期目标是让100-150名与会者就设计和合成理想的糖脂免疫刺激剂（可能是Galcer变体）交换意见。长期目标是更详细地了解这一重要生命过程的化学性质。讲座/讨论的形式将汇集大多数化学家，他们已经合成了几十种受海绵材料启发的小分子糖脂配体。为期一天的会议计划有14个讲座。每堂课之后都有一个讨论时间。这是有史以来第一次以糖脂免疫途径中至关重要的配体的设计和合成为重点的重大研讨会。本次研讨会将促进知识交流，这可能会导致在提高配体的可用性以精确控制免疫系统方面取得进展。国际化学家团体之间的开放思想交流，他们将与免疫学家互动，这也是一个好处。这种思想交流将加强美国的科学理想。自由、开放、不受约束的研究是科学造福社会的前进方向。由于海绵糖脂的免疫刺激作用的初步观察，其迷人的分子生物学已被阐明。糖脂作为连接抗原呈递细胞（APC）表面受体和自然杀伤T细胞（NKT）受体的“关键”。当apc -糖脂- nkt三元复合物形成时，细胞因子的爆发随之而来，这是最终免疫防御的信号。在合成化学家设计和合成母体海绵Galcer类似物的最初十几年里，研究计划主要是经验性的。配体与2种蛋白受体相互作用的结构特征尚未明确。2007年，三元配合物的x射线结构终于被报道出来。因此，化学家们有可能将观察到的氢键和范德华斥力结合到配合物中，作为设计新配体的一部分。最终目标是找到有利于诱导一种细胞因子的配体。在撰写本文时，尚不清楚哪种观察到的键合和/或排斥效应对哪种细胞因子具有决定性作用。研讨会讨论的一个计划成果是更好地理解这些细节。