Modulation of glyceraldehyde-3-phosphate dehydrogenase activity by surface functionalized quantum dots.
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 vitro activity 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.
Centre for Advanced Materials, Indian Association for the Cultivation of Science, Kolkata 700032, India. ghosh.srabanti@gmail.com camsa2@iacs.res.in.
Srabanti
S
Ghosh
Manju
M
Ray
Mahua Rani
MR
Das
Adrita
A
Chakrabarti
Ali Hossain
AH
Khan
D D
DD
Sarma
Somobrata
S
Acharya
D000818:Animals; D001672:Biocompatible Materials; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism*; D006019:Glycolysis; D064593:Heterografts; D051379:Mice; D045663:Quantum Dots; D012509:Sarcoma / Q000473:pathology
D001672:Biocompatible Materials; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases