9406656 Bullesbach Structurally related proteo-hormones of the insulin family consist of the parent hormone insulin, the hormone of pregnancy relaxin, and invertebrate developmental factors (i.e, bombyxin, isolated from the brains of the silk worm) and growth factors (i,e., molluscan insulin-related peptide, isolated from the pond snail). The wide variety of biological functions inherent in essentially the same three-dimensional structure implies that the biological function of this family of proteins depends primarily on the side chain distribution. It is the ultimate aim of this proposal to find the surface features that are crucial for the diverse biological functions of the insulin family of hormones. The initial step of this investigation involves the chemical synthesis of these factors and of defined analogs. The syntheses are based upon a novel approach, the site directed disulfide-bond formation, which has been highly successful in the synthesis of insulin-like structures. Investigation of the physical chemical and biological properties of the analogs by comparison with natural factors will give insight into the structure-function relationships within this important family of hormones. The long-term goal of these studies is a better understanding of the mode of action of hormones and the subsequent design and synthesis of mimetics. Such mimetics of hormones involved in invertebrate maturation may improve our ability to control insects by environmentally acceptable means, i.e., by suppressing or arresting the development of a specific pest. ***
