A computer screening approach to immunoglobulin superfamily structures and interactions: Discovery of small non-peptidic CD4 inhibitors as novel immunotherapeutics

• DOI: 10.1073/pnas.94.1.73
• Publication Date: 2002-07-26T14:31:39Z
• Authors: Song Li; Jimin Gao; Takashi Satoh; Thea M. Friedman; Andrea E. Edling; Ute Koch; Swati Choksi; Xiaobing Han; Robert Korngold; Ziwei Huang
• Keywords: Immunoglobulin superfamily

The interaction between CD4 and major histocompatibility complex (MHC) class II proteins is critical for the activation of + T cells, which are involved in transplantation reactions a number autoimmune diseases. In this study we have identified surface pocket as functional epitope implicated CD4–MHC T-cell activation. A computer-based strategy has been used to screen ≈150,000 non-peptidic organic compounds molecular data base identify group ligands proposed pocket. These small shown specifically block stable binding, exhibit significant inhibition immune responses animal models disease allograft transplant rejection, suggesting their potential novel immunosuppressants. This structure-based computer screening approach may general implications studying many immunoglobulin-like structures interactions that share similar structural features. Furthermore, results from demonstrated rational design inhibitors large protein–protein interfaces indeed be an achievable goal.