Hydrogen Bonding Constrains Free Radical Reaction Dynamics at Serine and Threonine Residues in Peptides

Free radical-initiated peptide sequencing (FRIPS) mass spectrometry derives advantage from the introduction of highly selective low-energy dissociation pathways in target peptides. An acetyl radical, formed at the peptide N-terminus via collisional activation and subsequent dissociation of a covalently attached radical precursor, abstracts a hydrogen atom from diverse sites on the peptide, yielding sequence information through backbone cleavage as well as side-chain loss. Unique free-radical-initiated dissociation pathways observed at serine and threonine residues lead to cleavage of the neighboring N-terminal C_α–C or N–C_α bond rather than the typical Cα–C bond cleavage observed with other amino acids. These reactions were investigated by FRIPS of model peptides of the form AARAAAXAA, where X is the amino acid of interest. In combination with density functional theory (DFT) calculations, the experiments indicate the strong influence of hydrogen bonding at serine or threonine on the observed free radical chemistry. Hydrogen bonding of the side-chain hydroxyl group with a backbone carbonyl oxygen aligns the singly occupied π orbital on the β-carbon and the N–C_α bond, leading to low-barrier β-cleavage of the N–C_α bond. Interaction with the N-terminal carbonyl favors a hydrogen-atom transfer process to yield stable c and z• ions, whereas C-terminal interaction leads to effective cleavage of the C_α–C bond through rapid loss of isocyanic acid. Dissociation of the C_α–C bond may also occur via water loss followed by β-cleavage from a nitrogen-centered radical. These competitive dissociation pathways from a single residue illustrate the sensitivity of gas-phase free radical chemistry to subtle factors such as hydrogen bonding that affect the potential energy surface for these low-barrier processes

Temperature Dependence of the Dissociative Electron Attachment to 2-Thiothymine

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Dissociative electron attachment to gas phase thiothymine: experimental and theoretical approaches

International audienceIn this contribution we have investigated experimentally and theoretically the interaction of low energy electrons with gas phase thiothymine (a sulphur containing analogue of thymine). We observe that the presence of the sulphur atom within thiothymine strongly controls the fragmentation dynamics. With the exception of the (M - H)(-) anion formation, the most favorable reaction channels are associated with a loss of sulphur containing negative fragments (i.e., the formation of S(-), SCN(-) and (M - S)(-)) suggesting that these resonances are localized at the C[double bond, length as m-dash]S group. Hence the present results demonstrate that certain reactions can be controlled by substitution of the sulphur atom at specific molecular sites within nucleobases. Our study thus represents a starting point for a physicochemical understanding of the action of sulphur-containing antimetabolites when used in chemoradiotherapy. Dissociative electron attachment to gas phase thiothymine: Experimental and theoretical approaches (PDF Download Available). Available from: http://www.researchgate.net/publication/260093855_Dissociative_electron_attachment_to_gas_phase_thiothymine_Experimental_and_theoretical_approache

Image Processing Methods for Diagnostic and Simulation Applications in Cardiology

The paper describes two particular applications of image processing for the purpose of analysis and simulation in the field of cardiology. The authors describe a method which allows for combining the 2D image obtained in ECHO examination, and a 3D model of heart, extracted from a set of CT slices. The fused image provides an intuitive view on the contractual function of heart, by overlaying the bull's eye diagram on the model of left ventricle. By preserving the spatial information, it is possible to accurately point the location of areas with impaired contractual function. Another method described by the authors, displays the use of the CT volume for simulation of echocardiography images for purpose of training application. A simple approach based on pixel brightness adaptation is used to provide images of sufficient training quality. At the same time authors highlight the issues of storage and run-time memory requirement of such application, and suggest a method of reducing the working set size

Computed tomography image processing for diagnostic and training applications in medicine

The paper deals with processing of imaging data obtained in the course of different medical examination procedures, for use in applications focused on improving both the diagnostic process of a patient as well as extending the training possibilities for medical personnel. Computed tomography (CT) data serves as the main source of structural and volumetric information. Fusion with left ventricular systolic function map, provides a vital information on the state of heart muscle. In parallel, the same set of computed tomography data is reused for simulation of trans-esophageal echocardiography (TEE). The presented simulation setup is used in the course of medical personnel training