Biomedical subjects

F H Laukien

Publications and source records attributed to F H Laukien.

3 recordsLinked to original sources

PubMed1999

Magnetic field gradients in solid state magic angle spinning NMR.

Magnetic field gradients have proven useful in NMR for coherence pathway selection, diffusion studies, and imaging. Recently they have been combined with magic angle spinning to permit high-resolution measurements of semi-solids, where magic angle spinning averages any residual dipolar couplings and local variations in the bulk magnetic susceptibility. Here we show the first examples of coherence pathway selection by gradients in dipolar coupled solids. When the gradient evolution competes with dipolar evolution the experiment design must take into account both the strength of the dipolar couplings and the means to refocus it. Examples of both homonuclear and heteronuclear experiments are shown in which gradients have been used to eliminate the need for phase cycling.

Glycine↗

PubMed1998

Rapid characterization of combinatorial libraries using electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry.

The relatively new field of combinatorial chemistry has enabled researchers to create large mixtures of compounds that can be screened for leads in developing potential drug candidates. The new synthetic method has also created a need for better procedures to analyze the complex mixtures that are generated. The immediate goal in most cases is to verify the synthetic procedure and to determine the purity and completeness of the library sample before binding studies are initiated. We report here a method to rapidly characterize small-molecule combinatorial libraries in solution. All combinatorial library samples were synthesized by combining a core molecule bearing two acid chloride functionalities with various amino acids to generate libraries of 36, 78 and 120 components. Using electrospray ionization fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS) we were able to identify 70-80% of the library components. All samples were analyzed as mixtures by direct infusion without chromatographic separation. Furthermore, nominally isobaric components could be resolved and identified through exact mass assignments without tandem mass spectrometery. ESI-FTICR-MS is a rapid and convenient tool for the characterization of small-molecule libraries. The method is especially useful for the analysis of larger libraries that contain many nominally isobaric components and impurities.

Chemistry, Pharmaceutical↗

PubMed1994

Deprotonation reactions of multiply protonated ubiquitin ions.

The gas-phase deprotonation reactions of multiply protonated ubiquitin ions have been studied in a Fourier-transform ion cyclotron resonance mass spectrometer. Electrospray ionization was used to generate ubiquitin ions with attachment of 7-13 protons. Rate constants were measured for the reactions of these protein ions with four amines: n-propylamine, di-n-propylamine, tri-n-propylamine, and N,N,N',N'-tetramethyl-1,4-diaminobutane. The gas-phase basicities of the amines ranged from 210.1 kcal/mol to 232.6 kcal/mol. The rate constants were found to increase as the charge state of the ion increased and as the basicity of the amine increased. Several reactions proceed at near the collision rate and have rate constants in excess of 10(-8) cm3 molecule-1 s-1. With the more basic reactants, multiple protons could be stripped sequentially from ubiquitin ions at roughly equivalent rates, suggesting that these protons are attached to sites with similar basicities. In general, deprotonation occurs if the gas-phase basicity of the amine is within 10 kcal/mol of the intrinsic gas-phase basicity of the amino acid residue being deprotonated. For [M+nH]n+, n = 4-6, nonlinear pseudo-first-order kinetic behavior indicated the presence of multiple ion structures. Kinetic, structural and thermodynamic aspects of these reactions are discussed.

Amines↗