Synthesis, Conformational Analysis, and Biological Activity of Proposed Vitronectin Antagonists

摘要

This project concerned the synthesis of a series of peptidomimetics, eventually directed toward drugs that would interfere with angiogenesis and therefore act as potential anticancer agents. The peptidomimetics, based on the beta-turn motif, contained a dipeptide core, which maps onto the central two residues of the naturally occurring turn, and a linker portion. The linker is necessary to enforce the desired turn type and to provide room for a third amino acid side chain mimic. In the reporting period, a series of linkers based on phenylalanine was prepared and inserted into the cyclic peptidomimetics. Once prepared, the resulting macrocycles were shown to adopt predominantly type II or II' turns, depending on the location of the phenylalanine side chain.