Project Title: 14. Seope: Molecular and Cellular Radiobiology Mechanisms of Action of Free Radicals and Hormones RX-03-02-(c) (Cont'd.) by pulse radiolysis with identification of putative free radicals of DPN and TPN coenzymes and related substituted nictinamide model compounds, and their possible involvement in enzyme reactions, (Borg) Research collaborators from the Department of Physiology of the Mount Sinai School of Medicine, have been working for some time to correlate the primary structure and conformation of neurohypophyseal hormones with their physiologic functions and metabolic fates. The various studies undertaken have lead to a proposed model for the conformation of oxytocin in solution, to a demonstration that certain distinguishing structural features of the neurohypophyseal hormones may serve as recognition sites for specific hormone-inactivating enzymes, and to a rationalization of many structureactivity functions. In order to prepare sophisticated hormone analogs for research and for therapeutic purposes, reflecting these insights, it has been necessary to devise new methods of peptide synthesis. In particular, new mild methods are being developed for the removal of amino-protecting groups and for the release of completed peptide products from solid supports in the solid phase method of peptide synthesis. 15. (Schwartz,Walter) Relationship to Other Projects: EPR has been used primarily in chemistry and physics, but applications to the life sciences have been increasing rapidly. It is not feasible to summarize here all of the work in these areas alone, nor are all the projects presently supported known to us. Moreover, the widespread occurrence in mature of free radical intermediates also makes relevant to this program a great volume of published work using procedures other than EPR; and it is not possible to review this material comprehensively either. However, on the basis of the known projects and the literature it is concluded that the instrumental developments in the BNL program involve little overlap with work elsewhere, and the major subject areas of BNL's biomedical work on free radical mechanisms are not directly duplicated. (Borg) The researches in solid phase peptide synthesis carried out at this lab- oratory are an integral part of a concerted affort to determine the molecular mechanism of hormone action and to apply such knowledge to medical pur . Although these studies are designed and undertaken with specific appligations in mind, the techniques being developed are of very broad appl alicy both in peptide synthesis and in other areas. The approach here in modifying peptide synthetic procedures is considered unique and is not known to be pursued in other laboratories. (See Continuation Sheet) 1149299 (Schwartz,Walter) RX-2_3