Sequestering ATP Inside Mitochondria by Nucleopeptide Induces Cancer Cell Apoptosis

Abstract

Mitochondria are essential organelles involving in cellular processes, especially adenosine triphosphate (ATP) production. ATP is a major energy source and can be a good eliminating target for anticancer therapy. We describe selective cancer treatment by sequestration of ATP and self-assemblies with ATP inside mitochondria using mitochondria-targeting nucleopeptide (MNP). We designed thymine containing MNP which can interact with ATP through electrostatic interaction and hydrogen bond between MNP and ATP. MNP exhibits selective higher binding affinity with ATP resulting in large complex and assemblies with ATP. MNP preferentially forms large assemblies with ATP even though MNP/ADP (adenosine diphosphate) complex is preformed after addition of ATP. Thus, sequestration of ATP and large assemblies of MNP/ATP inside mitochondria cause physical stress by large structures resulting in apoptosis.