This confederation of projects is concerned with the study of transformed cells. The goals of this highly integrated Program Project are to create peptidic forms of several classes of molecules that may aid in the development of an immune response to transformed cells or that might disable the transformed phenotype more effectively. The general principles that are addressed in this """"""""revised"""""""" program relate to the problem of tumor immunity and how to use small peptidic forms of macromolecular species to modify the transformed phenotype and growth of tumors. A group of scientists interested in the reduction of macromolecules into secondary structural forms with biological activity have been working together for several years. Now, under the auspices of a Program Project format, they will develop this well defined research focus involving multiple disciplines and varied aspects of immunology and cell biology into an inter-related and synergistic Program. The basic structural design of peptide forms and their improvement is guided by Greene, Murali, and Kieber-Emmons. All of these investigators have worked closely together for the last several years and are specialists in structural applications. In addition, an NMR specialist, Joshua Wand, will aid in the resolution of the atomic basis of the peptides' effects through the Structural Core which includes biophysical analysis of binding features as well as structural resolution units. The great immunologic strength in the areas of immunoglobulins and their application to tumors is aided by the laboratories of Ferrone, Greene, and Herlyn, experts in murine and human tumor immunology. The scientists involved in this Program all have worked in the general area of immunoglobulin function, and through these early efforts have come to focus on structural elements that guide immunity and receptor function. It is this process which has led to a focus on peptides which mimic secondary structural features. The use of peptidic mimics and linkers ultimately may have application to the treatment of human breast, lymphoid, and epithelial tumors.
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