Intra- and inter-metabolite correlation spectroscopy of tomato metabolomics data obtained by liquid chromatography-mass spectrometry and nuclear magnetic resonance

Nuclear magnetic resonance (NMR) and liquid chromatography-mass spectrometry (LCMS) are frequently used as technological platforms for metabolomics applications. In this study, the metabolic profiles of ripe fruits from 50 different tomato cultivars, including beef, cherry and round types, were recorded by both 1H NMR and accurate mass LC-quadrupole time-of-flight (QTOF) MS. Different analytical selectivities were found for these both profiling techniques. In fact, NMR and LCMS provided complementary data, as the metabolites detected belong to essentially different metabolic pathways. Yet, upon unsupervised multivariate analysis, both NMR and LCMS datasets revealed a clear segregation of, on the one hand, the cherry tomatoes and, on the other hand, the beef and round tomatoes. Intra-method (NMR¿NMR, LCMS¿LCMS) and inter-method (NMR¿LCMS) correlation analyses were performed enabling the annotation of metabolites from highly correlating metabolite signals. Signals belonging to the same metabolite or to chemically related metabolites are among the highest correlations found. Inter-method correlation analysis produced highly informative and complementary information for the identification of metabolites, even in de case of low abundant NMR signals. The applied approach appears to be a promising strategy in extending the analytical capacities of these metabolomics techniques with regard to the discovery and identification of biomarkers and yet unknown metabolites

Studies related to primitive chemistry. A proton and nitrogen-14 nuclear magnetic resonance amino acid and nucleic acid constituents and a and their possible relation to prebiotic

Preliminary proton nuclear magnetic resonance (NMR) studies were made to determine the applicability of this technique for the study of interactions between monomeric and polymeric amino acids with monomeric nucleic acid bases and nucleotides. Proton NMR results for aqueous solutions (D2O) demonstrated interactions between the bases cytosine and adenine and acidic and aromatic amino acids. Solutions of 5'-AMP admixed with amino acids exhibited more complex behavior but stacking between aromatic rings and destacking at high amino acids concentration was evident. The multisite nature of 5'-AMP was pointed out. Chemical shift changes for adenine and 5'-AMP with three water soluble polypeptides demonstrated that significant interactions exist. It was found that the linewidth-pH profile of each amino acid is unique. It is concluded that NMR techniques can give significant and quantitative data on the association of amino acid and nucleic acid constituents

Nuclear Magnetic Resonance: Applications to Organic Chemistry

From the preface: This brief book is the outgrowth of some forty lectures in which it was attempted to explain the phenomenon of nuclear magnetic resonance absorption and the uses of high-resolution nuclear magnetic resonance spectroscopy to organic chemists whose background, like that of the author, has often been deficient in nuclear and electromagnetic theory. Quite a number of suggestions were received for presentation of the material in printed form with illustrations based on the lecture slides. This has now been done, and it is hoped that the result will be of service to practicing chemists and students as a guide to various applications of NMR spectroscopy and an introduction to more authoritative works. Throughout, the coverage is illustrative rather than comprehensive. The author apologizes for choosing rather too many examples of applications from his own research, but it is always easiest to write about what one knows best. He is greatly indebted to Dr. W. D. Phillips of the E. I. du Pont Company for helping to kindle his interest in NMR research and to Dr. James N. Shoolery of Varian Associates and Professors V. Schomaker and H. M. McConnell for many patient hours of explanation with respect to both simple and difficult points of theory. The Office of Naval Research supported much of the research described herein which was carried out at the California Institute of Technology. Dr. Shoolery kindly supplied material for several of the figures, and Dr. Marjorie C. Caserio helped greatly with many of the details in getting the book together. Helpful suggestions were received from Professors D. Y. Curtin, R. Breslow, and D. E. Applequist. Professors William S. Johnson and E. E. van Tamelen supplied several unpublished spectra for Chapters 2 and 3. John D. Robert

Baryons 2002: Outlook

Summary and outlook presented at the 9th International Conference on the Structure of Baryons (BARYONS 2002), Jefferson Lab, March 3-8, 2002Comment: 10 pages, to be publ.in: Proceedings Int. Conf. BARYONS 2002, Jefferson Lab., March 200

Electron Spin Resonance Analysis of Cu(II) Coordination in Alzheimer's Disease-Related Peptides

We exploit electron spin resonance (ESR) to understand the Cu(II) coordination of Alzheimer's disease-related peptides. It has been observed that at a low level of Cu(II), the amyloid-β (Aβ) peptide forms fibrillar aggregates, whereas amorphous aggregates are dominant at a high level of Cu(II). Three histidine residues, His6, His13, and His14, are believed to be important to the interaction between Aâ and the metal ion. The role of each histidine residue in binding to Cu(II) has been controversial mainly due to the difficulty in elucidating the coordination environment of Cu(II) at physiological pH. Using pulsed ESR, we precisely examine the multiple histidine coordination in the Cu(II)-Aβ complex. For the first time, we provide direct evidence that all the three histidine residues coordinate to Cu(II) at physiological pH. Also, the relative contribution of the imidazole ring of each histidine residue to the Cu(II) coordination is quantified. To establish the relative contribution, we have developed a method that examines the effects of multiple histidine coordination on electron spin-echo modulation. The ESR results reveal that His13 and His14 simultaneously coordinate to Cu(II) in a significant fraction of the Cu(II)-Aβ complex at physiological pH. A broad interpretation of this result leads to the hypothesis that the simultaneous Cu(II)-coordination by the two adjacent residues retards the formation of the β-sheet structure and enables a substantial amount of amorphous aggregates to form.Next, we propose potential Cu(II)-binding motifs in tau protein based on the ESR spectra of some tau fragments. In tau protein, there are four pseudorepeats, each of which has a highly conserved 18-amino-acid segment. The ESR results show that the 18-amino-acid sequence in each pseudorepeat has a good binding affinity for Cu(II). In particular, pulsed ESR spectra reveal that a histidine residue and a backbone amide group are involved in the Cu(II) coordination and the presence of the intact N-terminus is essential for the stability of the complex. Also, given that the reported dissociation constants of some Cu(II)-peptide complexes vary by several orders of magnitude, we have developed a simple method to precisely compare the dissociation constants at physiological pH