CONFORMATION OF MITOGENIC PEPTIDE GROWTH FACTORS

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Mitogenic growth factors play a central role in the key biological processes of tissue growth, development, repair and maintenance. They have also been associated with neoplastic transformation in diseased states. The goal of this study is determination of the conformation of human epidermal growth factor (hEGF) to try to establish a relationship between its structure and function. The possibility of preserving the key structural features in fragments would then be examined as a basis of rational design of small molecule agonists or antagonists that would have therapeutic value. In this study the methodology of high-resolution NMR spectroscopy will be used, combining the techniques of proton homonuclear 2-dimensional NMR with new techniques for exploiting information from other nuclei present. The NMR experiments will be combined with chemical synthesis, using solid phase peptide synthesis, to prepare sufficient amounts of native peptides, analogues, and fragments and to incorporate stable isotopic labels such as 13C and 15N as NMR probes in determining the conformation.