Design, Synthesis and Study of Cell Adhesion Antagonists: Hydroxamate- Based Peptide Inhibitors of avb3 Integrin

摘要

Progress report of fellowship recipient describing the synthesis and results of biological testing of a hydroxamate based RGD peptide. The primary cause of death from breast cancer is the progression to metastatic disease. Two biological events that are essential for metastasis are the invasion of tumors to secondary sites and the growth of new blood vessels into the metastatic tumors. Both processes require a cell adhesion receptor called the alpha-v beta- 3 integrin. This receptor is expressed on metastatic breast cancer cells, where it has a role in mediating their migration to secondary sites. There is now great interest in applying small molecule antagonists of alpha-v beta-3 to prevent tumor progression and metastatic disease. This study is the preliminary test of a novel chemical approach toward the design of antagonists of the alpha- v beta-3 integrin.