Allosteric Sensing of Fatty Acid Binding by NMR: Application to Human Serum Albumin.
J Med Chem
; 59(16): 7457-65, 2016 08 25.
Article
in En
| MEDLINE
| ID: mdl-27429126
ABSTRACT
Human serum albumin (HSA) serves not only as a physiological oncotic pressure regulator and a ligand carrier but also as a biomarker for pathologies ranging from ischemia to diabetes. Moreover, HSA is a biopharmaceutical with a growing repertoire of putative clinical applications from hypovolemia to Alzheimer's disease. A key determinant of the physiological, diagnostic, and therapeutic functions of HSA is the amount of long chain fatty acids (LCFAs) bound to HSA. Here, we propose to utilize (13)C-oleic acid for the NMR-based assessment of albumin-bound LCFA concentration (CONFA). (13)C-Oleic acid primes HSA for a LCFA-dependent allosteric transition that modulates the frequency separation between the two main (13)C NMR peaks of HSA-bound oleic acid (ΔνAB). On the basis of ΔνAB, the overall [(12)C-LCFA]Tot/[HSA]Tot ratio is reproducibly estimated in a manner that is only minimally sensitive to glycation, albumin concentration, or redox potential, unlike other methods to quantify HSA-bound LCFAs such as the albumin-cobalt binding assay.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Serum Albumin
/
Oleic Acids
Limits:
Humans
Language:
En
Journal:
J Med Chem
Journal subject:
QUIMICA
Year:
2016
Document type:
Article
Affiliation country:
Canadá