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

Cuny Hunter College, New York NY

Investigators

Abstract

"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.