title: Optimization of xenon biosensors for detection of protein interactions.
abstract: Hyperpolarized 129Xe NMR spectroscopy can detect the presence of specific low-concentration biomolecular analytes by means of a xenon biosensor that consists of a water-soluble, targeted cryptophane-A cage that encapsulates the xenon. In this work, we use the prototypical biotinylated xenon biosensor to determine the relationship between the molecular composition of the xenon biosensor and the characteristics of protein-bound resonances. The effects of diastereomer overlap, dipole-dipole coupling, chemical-shift anisotropy, xenon exchange, and biosensor conformational exchange on the protein-bound biosensor signal were assessed. It was found that an optimal protein-bound biosensor signal can be obtained by minimizing the number of biosensor diastereomers and using a flexible linker of appropriate length. Both the line width and sensitivity of chemical shift to protein binding of the xenon biosensor were found to be inversely proportional to linker length.
authors.affiliation: Department of Chemistry, University of California at Berkeley, Berkeley, CA 94720, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Lowery
authors.forename: Sandra
authors.initials: S
authors.lastname: Garcia
authors.forename: Lana
authors.initials: L
authors.lastname: Chavez
authors.forename: E Janette
authors.initials: EJ
authors.lastname: Ruiz
authors.forename: Tom
authors.initials: T
authors.lastname: Wu
authors.forename: Thierry
authors.initials: T
authors.lastname: Brotin
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Dutasta
authors.forename: David S
authors.initials: DS
authors.lastname: King
authors.forename: Peter G
authors.initials: PG
authors.lastname: Schultz
authors.forename: Alex
authors.initials: A
authors.lastname: Pines
authors.forename: David E
authors.initials: DE
authors.lastname: Wemmer
mesh_terms: D001360:Avidin / Q000737:chemistry*; D015374:Biosensing Techniques / Q000379:methods* / Q000592:standards; D003903:Deuterium; D009682:Magnetic Resonance Spectroscopy / Q000379:methods / Q000592:standards; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D011487:Protein Conformation; D012015:Reference Standards; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014978:Xenon / Q000737:chemistry*; D014979:Xenon Isotopes
chemical_list: D014979:Xenon Isotopes; D001360:Avidin; D014978:Xenon; D003903:Deuterium