The objectives of this project are to establish the structural requirements for biological activity in the human glycoprotein hormones, luteinizing hormone (hLH) and human chorionic gonadotropin (hCG). Under Aim 1, using previous NMR structure of LMB (38-57) as a baseline, Dr. Keutmann will continue NMR analysis to define structure. They then will use a monoclonal antibody as a "surrogate receptor" in analysis of this ordered structure, in association with a binding site, using the technique of transferred nuclear-Overhauser effect spectroscopy. Under Aim 2, to define more fully the surface topography. Under Aim 2, to define more fully the surface topography of the receptor-associated peptide, they will determine the crystal structure of the loop in association with a Fab fragment of monoclonal antibody specific to the loop. Under Aim 3, they will use site-directed mutagenesis to verify that biologically- significant modifications in the peptide are also significant in the whole hormone, and might also exert effects on structure elsewhere in the overlapping adjacent regions.