We synthesized eight G8 molecular transporters (MTs) based on 4 different monosaccharide scaffolds, and studied their biological properties with a special focus on possible mitochondrial targeting and tissue selectivity. The mitochondrial affinity of these MTs was found to be clearly related to the scaffold stereochemistry and also tenuously with the lipophilicity. It may be suggested that in the practical delivery strategy of drugs for the brain and mitochondrial diseases the BBB permeability and mitochondrial affinity should be considered as key parameters, and that an enhanced mitochondrial affinity appears possible by further research on the structure-property relationship of guanidine-rich molecular transporters.
我们合成了八种基于四种不同
单糖支架的G8分子转运体(
MTs),并研究了它们的
生物特性,特别关注可能的线粒体靶向性和组织选择性。这些
MT的线粒体亲和力明显与支架的立体
化学相关,也与疏
水性有一定联系。可以建议,在针对大脑和线粒体疾病的药物实际递送策略中,应将血脑屏障渗透性和线粒体亲和力视为关键参数,并且通过进一步研究富含
胍的分子转运体的结构—性质关系,增强线粒体亲和力是可行的。