Mannose 6-phosphate mimics as potential ligands for the M6P-IGF2R

ORGN 137

Xiang Fei, feixiang629@hotmail.com1, Kaushik Panigrahi, kaushik@unlserve.unl.edu1, Christopher M. Connelly2, Richard G. MacDonald, rgmacdon@unmc.edu2, and David B. Berkowitz, dbb@unlserve.unl.edu1. (1) Department of Chemistry, University of Nebraska, Lincoln, NE 68588-0304, (2) Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198
The Insulin-like Growth Factor II Receptor (IGF2R) is known to bind a number of mannose 6-phosphate-decorated glycoproteins, at a site/sites distinct from the IFG2-binding site. In addition to serving a number of important housekeeping functions, the receptor appears to play a significant role in internalizing circulating IGF2. The potential interplay between ligand binding at the M6P-sites on the receptor and IGF2 binding/internalization has spurred interest in developing unnatural M6P-mimicking ligands for the receptor. This presentation will highlight our recent bioorganic, collaborative efforts at synthesizing hydrolytically stable M6P mimics that bind to the receptor. In particular, the installation of new phosphate-mimicking functionality on the mannopyranose core and attempts to exploit bivalency in ligand development will be discussed.
 

Total Synthesis, Materials, Devices and Switches, Molecular Recognition and Self-Assembly, Biologically-Related Molecules and Processes
8:00 PM-10:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Organic Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007