title: MR imaging of protein folding in vitro employing nuclear-Overhauser-mediated saturation transfer.
abstract: MR Z-spectroscopy allows enhanced imaging contrast on the basis of saturation transfer between the proton pools of cellular compounds and water, occurring via chemical exchange (chemical exchange saturation transfer, CEST) or dipole-dipole coupling (nuclear Overhauser effect, NOE). In previous studies, signals observed in the aliphatic proton region of Z-spectra have been assigned to NOEs between protons in water molecules and protons at the surface of proteins. We investigated a possible relationship between the signal strength of NOE peaks in Z-spectra obtained at B0 = 7 T and protein structure. Here, we report a correlation of NOE-mediated saturation transfer with the structural state of bovine serum albumin (BSA), which was monitored by fluorescence spectroscopy. Encouraged by CEST signal changes observed in tumor tissue, our observation also points to a possible contrast mechanism for MRI sensitive to the structural integrity of proteins in cells. Therefore, protein folding should be considered as an additional property affecting saturation transfer between water and proteins, in combination with the microenvironment and physiological quantities, such as metabolite concentration, temperature and pH.
authors.affiliation: Department of Medical Physics in Radiology, Deutsches Krebsforschungszentrum (DKFZ) [German Cancer Research Center], Heidelberg, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Zaiss
authors.forename: Patrick
authors.initials: P
authors.lastname: Kunz
authors.forename: Steffen
authors.initials: S
authors.lastname: Goerke
authors.forename: Alexander
authors.initials: A
authors.lastname: Radbruch
authors.forename: Peter
authors.initials: P
authors.lastname: Bachert
mesh_terms: D000328:Adult; D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology; D002417:Cattle; D005260:Female; D005453:Fluorescence; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D011489:Protein Denaturation / Q000187:drug effects; D017510:Protein Folding / Q000187:drug effects; D058767:Protein Unfolding / Q000187:drug effects; D012710:Serum Albumin, Bovine / Q000378:metabolism; D014508:Urea / Q000494:pharmacology
chemical_list: D012710:Serum Albumin, Bovine; D014508:Urea
keywords: MRI; bovine serum albumin (BSA); brain tumors; cancer; chemical exchange saturation transfer (CEST); nuclear Overhauser effect (NOE); protein folding