Characterization of the effects of nonspecific xenon-protein interactions on 129Xe chemical shifts in aqueous solution:: Further development of xenon as a biomolecular probe

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.