CONFORMATION OF MITOGENIC PEPTIDE GROWTH FACTORS

促有丝分裂生长因子在关键的生物学过程中起着核心作用。 组织生长、发育、修复和维护的过程。 它们也与肿瘤转化有关， 病态的国家 本研究的目标是确定 人表皮生长因子（hEGF）的构象，试图 建立其结构和功能之间的关系。 的 在碎片中保留关键结构特征的可能性 然后将作为合理设计的基础进行审查， 分子激动剂或拮抗剂， 值 本研究采用高分辨核磁共振技术， 将使用光谱学，结合质子技术， 二维核磁共振新技术 利用其他原子核的信息 的NMR 实验将与化学合成相结合，使用固体 阶段肽合成，以制备足够量的天然肽。 肽、类似物和片段，并将稳定的 13 C和15 N等同位素标记物作为核磁共振探针用于测定 conformance.

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.