小肽修饰的PAMAM树枝状化合物的生物活性

THE BIOACTIVITY OF PAMAM DENDRIMERS MODIFIED WITH PEPTIDES

合成了甘氨酸 (Gly) 天冬氨酸 (Asp)组成的肽链Gly Asp、Gly Asp Gly Asp、Gly Asp (Gly Asp) 2 .分别将天冬氨酸及上述合成的肽链引入到聚酰胺 胺型树枝状化合物 (PAMAM)的表面 .对所得化合物进行了分子模拟 ,结果表明Gly Asp (Gly Asp) 2 肽链在PAMAM表面可形成接近于 β sheet的构象 .由实验得知 ,经Asp、Gly Asp、Gly Asp Gly Asp、Gly Asp (Gly Asp) 2 修饰的PAMAM树枝状化合物对抗坏血酸还原FeⅢ 细胞色素C(cytc)的反应有干扰作用 ,导致该反应速率下降 .这说明所合成的化合物与cytc有较好的结合能力 .特别是Gly Asp (Gly Asp) 2 修饰的PAMAM ,其与cytc的结合常数为 1 6ⅹ 1 0 5.

The peptides of Gly-Asp, Gly-Asp-Gly-Asp and Gly-Asp-(Gly-Asp), were synthesized. These peptides and Asp were introduced at the periphery of G3. 5 PAMAM dendrimers, respectively. It was found by calculating from H-1 integrations of each modified compound that 77 %, 60 %, 24 % and 18 % of ester groups on the surface of these dendrimers reacted with the Asp,Gly-Asp, Gly-Asp-Gly-Asp and Gly-Asp-(Gly-Asp), peptides, respectively. The molecular simulating showed that the conformation of Gly-Asp-(Gly-Asp), is quite similar to beta-sheets. Compared with PAMAMC,these modified PAMAM dendrimers could obviously decrease the reduction rate of Fe-III-cyt c by ascorbic acid, especially, the dendrimer with Gly-Asp-( Gly-Asp), on its exterrior. The experimental results demonstrated the better recognition and affinity between the peptides modified PAMAM dendrimers and Cytochrome C. The association constant of G3.5-Gly-Asp-(Gly-Asp)(2) with cytochrome C is 1.6 x 10(5).