Title
Modulation of glyceraldehyde-3-phosphate dehydrogenase activity by surface functionalized quantum dots
Author
Srabanti Ghosh, Manju Ray, Mahua Rani Das, Adrita Chakrabarti, Ali Hossain Khan, D. D. Sarma, Somobrata Acharya
Year
2014
Journal
Physical Chemistry Chemical Physics
Abstract
Enzymatic regulation is a fast and reliable diagnosis tool via identification and design of inhibitors for modulation of enzyme function. Previous reports on quantum dots (QDs)–enzyme interactions reveal a protein-surface recognition ability leading to promising applications in protein stabilization, protein delivery, bio-sensing and detection. However, the direct use of QDs to control enzyme inhibition has never been revealed to date. Here we show that a series of biocompatible surface-functionalized metal–chalcogenide QDs can be used as potent inhibitors for malignant cells through the modulation of enzyme activity, while normal cells remain unaffected. The in vitroactivity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), an enzyme involved critically in the glycolysis of cancer cells, is inactivated selectively in a controlled way by the QDs at a significantly low concentration (nM). Cumulative kinetic studies delineate that the QDs undergo both reversible and irreversible inhibition mechanisms owing to the site-specific interactions, enabling control over the inhibition kinetics. These complementary loss-of-function probes may offer a novel route for rapid clinical diagnosis of malignant cells and biomedical applications.
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Ligand binding, Materials, Biochemistry