@article {325, title = {Development of a functionalized xenon biosensor}, journal = {Journal of the American Chemical Society}, volume = {126}, year = {2004}, note = {J Am Chem Soc872UHTimes Cited:60Cited References Count:76}, month = {Nov 24}, pages = {15287-15294}, abstract = {

NMR-based biosensors that utilize laser-polarized xenon offer potential advantages beyond current sensing technologies. These advantages include the capacity to simultaneously detect multiple analytes, the applicability to in vivo spectroscopy and imaging, and the possibility of \"remote\" amplified detection. Here, we present a detailed NMR characterization of the binding of a biotin-derivatized caged-xenon sensor to avidin. Binding of \"functionalized\" xenon to avidin leads to a change in the chemical shift of the encapsulated xenon in addition to a broadening of the resonance, both of which serve as NMR markers of ligand-target interaction. A control experiment in which the biotin-binding site of avidin was blocked with native biotin showed no such spectral changes, confirming that only specific binding, rather than nonspecific contact, between avidin and functionalized xenon leads to the effects on the xenon NMR spectrum. The exchange rate of xenon (between solution and cage) and the xenon spin-lattice relaxation rate were not changed significantly upon binding. We describe two methods for enhancing the signal from functionalized xenon by exploiting the laser-polarized xenon magnetization reservoir. We also show that the xenon chemical shifts are distinct for xenon encapsulated in different diastereomeric cage molecules. This demonstrates the potential for tuning the encapsulated xenon chemical shift, which is a key requirement for being able to multiplex the biosensor.

}, keywords = {drug discovery}, isbn = {0002-7863}, doi = {Doi 10.1021/Ja0483037}, url = {://WOS:000225233600051}, author = {Spence, M. M. and Ruiz, E. J. and Rubin, S. M. and Lowery, T. J. and Winssinger, N. and Schultz, P. G. and Wemmer, D. E. and Pines, A.} } @article {340, title = {Amplification of xenon NMR and MRI by remote detection}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {100}, year = {2003}, note = {P Natl Acad Sci USA709HPTimes Cited:65Cited References Count:28}, month = {Aug 5}, pages = {9122-9127}, abstract = {

A technique is proposed in which an NMR spectrum or MRI is encoded and stored as spin polarization and is then moved to a different physical location to be detected. Remote detection allows the separate optimization of the encoding and detection steps, permitting the independent choice of experimental conditions and excitation and detection methodologies. In the initial experimental demonstration of this technique, we show that taking dilute Xe-129 from a porous sample placed inside a large encoding coil and concentrating it into a smaller detection coil can amplify NMR signal. In general, the study of NMR active molecules at low concentration that have low physical filling factor is facilitated by remote detection. In the second experimental demonstration, MRI information encoded in a very low-field magnet (4-7 mT) is transferred to a high-field magnet (4.2 T) to be detected under optimized conditions. Furthermore, remote detection allows the utilization of ultrasensitive optical or superconducting quantum interference device detection techniques, which broadens the horizon of NMR experimentation.

}, keywords = {field}, isbn = {0027-8424}, doi = {Doi 10.1073/Pnas.1133497100}, url = {://WOS:000184620000007}, author = {Moule, A. J. and Spence, M. M. and Han, S. I. and Seeley, J. A. and Pierce, K. L. and Saxena, S. and Pines, A.} } @conference {355, title = {"Lighting Up" NMR and MRI in Colloidal and Interfacial Systems}, booktitle = {Magnetic Resonance in Colloid and Interface Sciences}, year = {2002}, month = {2002}, pages = {97-106}, publisher = {Kluwer Academic Publishers, Netherlands}, organization = {Kluwer Academic Publishers, Netherlands}, address = {St. Petersburg, Russia}, author = {Pines, A. and Logan, J.W. and Spence, M. M.}, editor = {J. Fraissard and O. Lapina, eds} } @article {366, title = {Characterization of the effects of nonspecific xenon-protein interactions on Xe-129 chemical shifts in aqueous solution: Further development of xenon as a biomolecular probe}, journal = {Journal of Magnetic Resonance}, volume = {152}, year = {2001}, note = {J Magn Reson472QDTimes Cited:37Cited References Count:34}, month = {Sep}, pages = {79-86}, abstract = {

The sensitivity of Xe-129 chemical shifts to weak nonspecific xenon-protein interactions has suggested the use of xenon to probe biomolecular structure and interactions. The realization of this potential necessitates a further understanding of how different macromolecular properties influence the Xe-129 chemical shift in aqueous solution. Toward this goal, we have acquired Xe-129 NMR spectra of xenon dissolved in amino acid, peptide, and protein solutions under both native and denaturing conditions. In general, these cosolutes induce Xe-129 chemical shifts that are downfield relative to the shift in water, as they deshield the xenon nucleus through weak, diffusion-mediated interactions. Correlations between the extent of deshielding and molecular properties including chemical identity, structure, and charge are reported. Xenon deshielding was found to depend linearly on protein size under denaturing solution conditions; the denaturant itself has a characteristic effect on the Xe-129 chemical shift that likely results from a change in the xenon solvation shell structure. In native protein solutions, contributions to the overall Xe-129 chemical shift arise from the presence of weak xenon binding either in cavities or at the protein surface. Potential applications of xenon as a probe of biological systems including the detection of conformational changes and the possible quantification of buried surface area at protein-protein interfaces are discussed. (C) 2001 Academic Press.

}, keywords = {gas}, isbn = {1090-7807}, doi = {Doi 10.1006/Jmre.2001.2389}, url = {://WOS:000170995700009}, author = {Rubin, S. M. and Spence, M. M. and Pines, A. and Wemmer, D. E.} } @article {367, title = {Detection of a conformational change in maltose binding protein by Xe-129 NMR spectroscopy}, journal = {Journal of the American Chemical Society}, volume = {123}, year = {2001}, note = {J Am Chem Soc467XNTimes Cited:28Cited References Count:28}, month = {Sep 5}, pages = {8616-8617}, keywords = {blood}, isbn = {0002-7863}, doi = {Doi 10.1021/Ja0110325}, url = {://WOS:000170729200029}, author = {Rubin, S. M. and Spence, M. M. and Dimitrov, I. E. and Ruiz, E. J. and Pines, A. and Wemmer, D. E.} } @article {364, title = {Functionalized xenon as a biosensor}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {98}, year = {2001}, note = {P Natl Acad Sci USA472CZTimes Cited:112Cited References Count:29}, month = {Sep 11}, pages = {10654-10657}, abstract = {

The detection of biological molecules and their interactions is a significant component of modern biomedical research. In current biosensor technologies, simultaneous detection is limited to a small number of analytes by the spectral overlap of their signals. We have developed an NMR-based xenon biosensor that capitalizes on the enhanced signal-to-noise, spectral simplicity, and chemical-shift sensitivity of laser-polarized xenon to detect specific biomolecules at the level of tens of nanomoles. We present results using xenon \"functionalized\" by a biotin-modified supramolecular cage to detect biotin-avidin binding. This biosensor methodology can be extended to a multiplexing assay for multiple analytes.

}, keywords = {mri}, isbn = {0027-8424}, doi = {Doi 10.1073/Pnas.191368398}, url = {://WOS:000170966800030}, author = {Spence, M. M. and Rubin, S. M. and Dimitrov, I. E. and Ruiz, E. J. and Wemmer, D. E. and Pines, A. and Yao, S. Q. and Tian, F. and Schultz, P. G.} } @article {375, title = {Evidence of nonspecific surface interactions between laser-polarized xenon and myoglobin in solution}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {97}, year = {2000}, note = {P Natl Acad Sci USA345XMTimes Cited:40Cited References Count:35}, month = {Aug 15}, pages = {9472-9475}, abstract = {

The high sensitivity of the magnetic resonance properties of xenon to its local chemical environment and the large Xe-129 NMR signals attainable through optical pumping have motivated the use of xenon as a probe of macromolecular structure and dynamics. In the present work, we report evidence for nonspecific interactions between xenon and the exterior of myoglobin in aqueous solution, in addition to a previously reported internal binding interaction. Xe-129 chemical shift measurements in denatured myoglobin solutions and under native conditions with varying xenon concentrations confirm the presence of nonspecific interactions. Titration data are modeled quantitatively with treatment of the nonspecific interactions as weak binding sites. Using laser-polarized xenon to measure Xe-129 spin-lattice relaxation times (T-1), we observed a shorter T-1 in the presence of 1 mM denatured apomyoglobin in 6 M deuterated urea (T-1 = 59 +/- 1 s) compared with that in 6 M deuterated urea alone (T-1 = 291 +/- 2 s), suggesting that nonspecific xenon-protein interactions can enhance Xe-129 relaxation. An even shorter T1 was measured in ? mM apomyoglobin in D2O (T-1 = 15 +/- 0.3 s), compared with that in D2O alone (T-1 = 506 +/- 5 s). This difference in relaxation efficiency likely results from couplings between laser-polarized xenon and protons in the binding cavity of apomyoglobin that may permit the transfer of polarization between these nuclei via the nuclear Overhauser effect.

}, keywords = {binding}, isbn = {0027-8424}, doi = {Doi 10.1073/Pnas.170278897}, url = {://WOS:000088840500026}, author = {Rubin, S. M. and Spence, M. M. and Goodson, B. M. and Wemmer, D. E. and Pines, A.} }