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

“糖脂免疫刺激剂”是美国化学学会波士顿2015年全国会议上举行的一个研讨会。导致这次研讨会的创始发现发生在20年前，当时科学家从冲绳的一块海绵中分离出了一个小家族的半乳糖神经酰胺(Galcers)。令人惊讶的是，Galcers可以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名与会者就理想的糖脂免疫刺激剂(可能是Galercer的变种)的设计和合成交换意见。更长期的目标是更详细地了解这一重要生命过程的化学成分。讲座/讨论形式将汇集大多数化学家，他们已经合成了数十个受海绵材料启发的小分子糖脂配体。为期一天的课程计划有14场讲座。每堂课之后都有一段讨论时间。这是有史以来第一次主要的研讨会，焦点是设计和合成对基于糖脂的免疫途径至关重要的配体。这次研讨会将促进智力交流，这可能会导致在提高配体的可用性方面取得进展，以精确控制免疫系统。国际化学家小组之间的公开思想交流也是一个好处，他们随后将与免疫学家互动。思想交流将强化美国的科学理想。自由、开放和不受约束的研究是科学造福社会的方向。自从最初观察到海绵糖脂的免疫刺激作用以来，它们迷人的分子生物学已经被阐明。糖脂是连接抗原提呈细胞(APC)表面受体和自然杀伤T细胞(NKT)受体的关键。当APC-糖脂-NKT三元复合体形成时，随之而来的是一系列细胞因子，这是最终免疫防御的信号。在合成化学家设计和合成亲本海绵Galercer类似物的最初十几年里，研究计划主要是经验性的。该配体与两种蛋白受体相互作用的结构特征尚未确定。2007年，该三元络合物的X射线结构终于被报道。因此，化学家有可能将观察到的氢键和范德华斥力纳入络合物中，作为新配体设计的一部分。最终的目标是拥有有利于诱导一种细胞因子的配体。在撰写本文时，还不清楚观察到的结合和/或排斥效应中的哪一种对哪种细胞因子具有决定性作用。专题讨论会讨论的一个计划成果是更好地了解这些细节。

"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.