Reverse Engineering the Intracellular Self-Assembly of a Functional Mechanopharmaceutical Device.

ABSTRACT: Weakly basic, poorly soluble chemical agents could be exploited as building blocks for constructing sophisticated molecular devices inside the cells of living organisms. Here, using experimental and computational approaches, we probed the relationship between the biological mechanisms mediating lysosomal ion homeostasis and the self-assembly of a weakly basic small molecule building block (clofazimine) into a functional, mechanopharmaceutical device (intracellular Crystal-Like Drug Inclusions - "CLDIs") in macrophage lysosomes. Physicochemical considerations indicate that the intralysosomal stabilization of the self-assembled mechanopharmaceutical device depends on the pHmax of the weakly basic building block and its affinity for chloride, both of which are consistent with the pH and chlor

SUBMITTER: Woldemichael T 

PROVIDER: S-EPMC5811454 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature