Mesa-Antunez Pablo, Collado Daniel, Vida Yolanda, Najera Francisco, Fernandez Tahia, Torres Maria Jose, Perez-Inestrosa Ezequiel
Department of Organic Chemistry, University of Malaga, IBIMA, 29071 Malaga, Spain.
Andalusian Centre for Nanomedicine and Biotechnology- BIONAND, Parque Tecnologico de Andalucia, 29590 Malaga, Spain.
Polymers (Basel). 2016 Mar 26;8(4):111. doi: 10.3390/polym8040111.
A new fluorescent dendrimeric antigen (DeAn) based on a dendron with amoxicilloyl terminal groups was synthesized. The synthesis was carried out using a novel class of all-aliphatic polyamide dendrimer (BisAminoalkylPolyAmide Dendrimers, or BAPAD) involving the direct condensation of 3,3'-diazidopivalic acid as a building block. Iterative azide reduction/amide formation increases the dendrimer generation. The BAPAD dendrimer was designed with a cystamine core. Reduction of the disulfide bond allows the incorporation of BAPAD dendrons into a 1,8-naphthalimide functionalized with a maleimide group. The fluorescence properties of DeAn were studied in PBS and compared with the properties of an equivalent dendron possessing amino-terminal groups. Both molecules shown high fluorescence quantum yields in PBS and could readily be visualized by fluorescence microscopy. DeAn was used as a synthetic antigen in a biomedical assay that tests their potential as an amoxicillin carrier in drug internalization by dendritic cells (DC) from tolerant and allergic patients. Cytometry data suggest that the dendrons are non-toxic and easily internalized by DCs, while confocal microscopy images indicate that the compounds are preferentially accumulated in the cytoplasm. These results indicate that BAPAD dendrons are good candidates for synthetic scaffolds for biomedical applications.
合成了一种基于具有阿莫西林酰基端基的树枝状分子的新型荧光树枝状抗原(DeAn)。合成过程使用了一类新型的全脂肪族聚酰胺树枝状大分子(双氨基烷基聚酰胺树枝状大分子,或BAPAD),该过程涉及以3,3'-二叠氮基新戊酸作为结构单元的直接缩合反应。叠氮基还原/酰胺形成的迭代过程增加了树枝状大分子的代数。BAPAD树枝状大分子设计有胱胺核心。二硫键的还原使得BAPAD树枝状分子能够掺入用马来酰亚胺基团功能化的1,8-萘二甲酰亚胺中。在磷酸盐缓冲盐溶液(PBS)中研究了DeAn的荧光特性,并将其与具有氨基端基的等效树枝状分子的特性进行了比较。两种分子在PBS中均显示出高荧光量子产率,并且可以通过荧光显微镜轻松观察到。DeAn在生物医学检测中用作合成抗原,该检测测试了它们作为阿莫西林载体在来自耐受性和过敏性患者的树突状细胞(DC)药物内化中的潜力。细胞计数数据表明,树枝状分子无毒且易于被DC内化,而共聚焦显微镜图像表明这些化合物优先积聚在细胞质中。这些结果表明,BAPAD树枝状分子是生物医学应用合成支架的良好候选者。