This broadly titled project has over the years covered all my major research interests and represented my only source of research support. According to my current understanding of this field, and based on recent research developments and interest, I judge that the most important area for me to pursue at this time, is the area of covalent protein structure as it relates to all aspects of biological function. This recent rekindling of my interest in covalent structure is in part derived from the realization of how extensive the in vivo post-translational modificaton of the original polypeptide synthesized from 20 amino is. We can identify about 130 different derivatized amino acids in different proteins at this time, and considering that each one of these derivatives must have been selected to fulfill specific functional roles, this area represents a long list of important unanswered questions. The specific systems and problems that will be pursued in the next several years are: I. The biological roles of the glycosyl moieties in glycoproteins based on the fundamental hypothesis that there exists a universal "language" of cell-cell and cell-molecule communication based on specific lectin-oligosaccharide interactions; II. The specificity determinants in in vivo modification of specific proteins (N-terminal modification of pancreatic alpha-amylase and muscle enolase, the formation of ornithine in soybean lectins and epsilon(gamma-glltamyl)-lysine cross-link formation catalyzed by transglutaminase); III. The relation of primary structure to sub-unit interaction, metal binding and active site structure in enolases. The problems will be tackled primarily by establlshed methods, some of which have been developed in the past through work supported by this grant, but the exploration of new methodology will continue to be a significant component of this project. I also intend to continue to explore the direct application of new knowledge in the 3 proposed problem areas to such important practical problems as enzyme stabilization and protection for enzyme replacement therapy and the role of lectin-saccharide interactions in host-parasite or host-symbiote interactions in normal and pathological conditions.