小肽修饰的PAMAM树枝状化合物的生物活性

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 BIOACTIVITY OF PAMAM DENDRIMERS MODIFIED WITH PEPTIDES

The peptides of Gly-Asp,Gly-Asp-Gly-Asp and Gly-Asp-(Gly-Asp) 2 were synthesized.These peptides and Asp were introduced at the periphery of G3.5 PAMAM dendrimers,respectively.It was found by calculating from 1H 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) 2 peptides,respectively.The molecular simulating showed that the conformation of Gly-Asp-(Gly-Asp) 2 is quite similar to β-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) 2 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 1.6×10 5.