Search for the anti-tumor derivatives containing the somatostatin sequence focusing on the hydrophobic index

构效关系研究表明YO-14的疏水性可能是其抗增殖活性的主要原因。本项目利用生长抑素序列、X-TyrD-Trp-Y和肽合成技术对这一假设进行了探索：(1)取代Tyr产生了比YO-14更疏水的YO化合物，具有更高的抗增殖活性；(2)双置换（X-Tyr-Ile-NH-aphthalene）产生了一种有效的ss特异性DNA极化抑制剂；(3)含有荧光NBD的YO化合物的分布表明，金刚烷部分具有良好的渗透性。

A structure-activity relationship studies revealed that hydrophobicity of YO-14 could be responsible for their antiproliferative activity. Thishypothesis has been explored in this project using the somatostatin sequence,X-TyrD-Trp-Y, and peptide synthesis technique: (1) substitution of Tyr produced morehydrophobic YO compounds with higher antiproliferative activity than YO-14;(2) double replacement (X-Tyr-Ile-NH-aphthalene) created a potent and ss -specific DNA polinhibitor; (3)the distribution of YO compounds incorporated fluorescent NBD, demonstrated that an adamantane moiety had an excellent permeability.