Synthesis and Characterization of MOG-IDAC and PLP-PEG-B7AP Molecules for Efficacy Evaluation in the EAE mouse model

Abstract

Synthesis, Formulation, and In vivo Evaluation of MOG-PEG-IDAC and PLP-PEG-B7AP for Targeting APC to Suppress EAE John M. Stewart, Crisandra Wilkie, Barlas Buyuktimkin, Ahmed Badawi, Paul Kiptoo, and Teruna J. Siahaan Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence KS, 66047 There are two long-term objective of this project 1. Is to use a novel I-Domain Antigen Conjugate (IDAC) molecule to target antigenic peptide to APC to control autoimmune diseases. The short-term objectives of this project are to synthesize, formulate, and evaluate the efficacy of Myelin Oligodendrocyte Glycoprotein (MOG) MOG-PEG-IDAC molecules in suppressing Experimental Autoimmune Encephalomyelitis (EAE) in animal models. The MOG-PEG-IDAC molecule is hypothesized to simultaneously bind to major histocompatibility complex II (MHC-II) and intercellular adhesion molecule 1 (ICAM-1) on the surface of antigen-presenting cells (APC). 2. Is to evaluate the efficacy of PLP-PEG-B7AP in suppressing EAE in mice. The PLP-PEG-B7AP molecule is hypothesized to simultaneously bind to the MHC-II and B7 molecule on the surface of the APC. This binding blocks the formation of the "immunological synapse" and will generate the regulatory response to suppress EAE. Two specific aims are proposed to carry out the short-term objectives. The first specific aim is to design MOG-PEG-IDAC molecules. The second specific aim is to evaluate the efficacy of PLP-PEG-B7AP in suppressing EAE in animal models. To date, the synthesis and characterization of the MOG-PEG-IDAC has been completed, along with EAE animal studies of the PLP-PEG-B7AP.