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F W McLafferty

Publications and source records attributed to F W McLafferty.

11 recordsLinked to original sources
PubMed1992

High-resolution tandem mass spectrometry of large biomolecules.

Unit-resolution mass spectra have been obtained for peptides as large as 17 kDa, providing information on impurities and adduct ions, as well as accurate molecular weight values. Electrospray ionization produces many multiply-charged species of the same mass; isotopic peak resolution provides direct charge state assignment from the unit mass spacing of the isotopes. This is of special value when the spectrum also has many masses, such as from precursor ion dissociation or impurities. Mass measuring errors not only are concomitantly lower (less than 0.1 Da) than when the isotopic peaks are unresolved but also are independent of variations in 13C/12C natural isotopic abundances. Also, larger errors are avoided that occur when the measured peak envelope includes impurity or adduct ions. This also benefits tandem mass spectrometry; dissociation of peptide ions as large as 8.5 kDa yields fragment masses consistent (less than 0.1 Da) with their amino acid sequences.

Albumins↗
PubMed1990

Hadamard transform measurement of tandem Fourier-transform mass spectra.

The simultaneous collection of multiple spectra using tandem (MS/MS) and multidimensional (MS/MS/MS) mass spectrometry from multiple precursors is demonstrated to yield correspondingly enhanced sensitivity. This approach utilizes Hadamard transform deconvolution and takes advantage of the multichannel dissociation capability of Fourier-transform mass spectrometry. By application of this to an 11-component mixture, the 11 spectra of the products of dissociating 11 different combinations of six of the component molecular ions are measured; Hadamard transformation yields individual spectra of the precursor ions exhibiting a signal-to-noise improvement of 1.8x over spectra measured separately, as predicted by theory. Precursor ion selection with high specificity and product formation with high abundance reproducibility are critical; spurious peaks resulting from imperfect reproducibility can be minimized by using simultaneous equation coefficients reflecting the degree of precursor dissociation. Extension of this technique to MSn spectra is demonstrated with simultaneous MS/MS/MS monitoring of three precursors and three daughters yielding nine spectra representing the nine possible dissociation pathways. For MSn spectra, coding the product relationships for each additional step (e.g., precursor----daughter, daughter----granddaughter) requires elimination of half of the remaining ions. No ions are lost for coding in an improved Hadamard approach in which the combined daughter spectrum of the selected half of the precursors is subtracted from that of the other half.

Fourier Analysis↗
PubMed1990

Studies of unusual simple molecules by neutralization-reionization mass spectrometry.

Reactive or unstable molecules are key intermediates in many important reactions, but can be difficult to prepare for experimental studies. Species with missing (:CH-OH) or extra (H3) substituents can often be formed conveniently in the gas phase by neutralizing a beam of a more stable ionic counterpart (CH = O+H, H3+). Reionization of the neutral after approximately 10(-6) seconds tests its stability, whereas its unimolecular chemistry can be probed by preparing it with different amounts of internal energy. The resulting neutral products are reionized and mass analyzed. Isomers are then characterized by ion dissociation and a third mass-analysis step. Many unusual molecules have been characterized with this technique, which can also be used to probe complex unimolecular chemistry, such as that of cyclobutadiene and ethylene oxide.

Butadienes↗
PubMed1989

Fourier-transform mass spectrometry of large molecules by electrospray ionization.

The multiply charged ions produced by electrospray ionization of peptides of molecular masses up to 29 kDa have been successfully introduced into a Fourier transform mass spectrometer of unique capabilities for tandem mass spectrometry, large ion dissociation, and resolution. Electrospray ionization places an unusually high number of charges on a peptide yielding mass/charge (m/z) values of 600-1500; in this range at normal operating pressures (approximately 10(-9) torr; 1 torr = 133.3 Pa) Fourier-transform mass spectrometry resolving power is greater than 100,000. Although only 10(-7) torr pressure has been obtained with the initial interface, the resulting resolving power of 5000 makes possible the resolution of isotopic peaks of multiply charged ions. Mass measuring accuracies of a few daltons for molecular masses up to 17 kDa have also been achieved.

Enzymes↗
PubMed1985

Peptide mixture sequencing by tandem Fourier-transform mass spectrometry.

Picomole samples of the linear peptide gramicidin D and cyclic peptide gramicidin S are shown to be impure by the laser-desorption formation of multiple groups of molecular adduct peaks by using Fourier-transform mass spectrometry. Selective excitation of the molecular peaks of the major sample component followed by collisionally activated dissociation provides complete sequence information for the cyclic decapeptide and for 12 of the 15 amino acids of the linear peptide. This instrumentation shows striking advantages in sensitivity, resolution, and mass accuracy in comparison to tandem mass spectrometers used previously.

Amino Acid Sequence↗
PubMed1978

Polypeptide sequencing by liquid chromatography mass spectrometry.

Key steps in a proposed automated system for polypeptide sequencing utilizing a liquid chromatograph mass spectrometer computer system have been tested with mixtures containing up to six model oligopeptides. At the low nanomole level it was possible to obtain complete sequence information for all components in many, but not all, of the mixtures tried. Interpretation of the results is complicated by the presence of numerous side-products formed in the derivatization process. Minimization of such impurities will be necessary to reduce the ambiguity of the sequence information resulting from more complex mixtures, such as those expected from the degradation of larger polypeptides, and to reduce sample requirements to the subnanomole level. However, the present system appears to have unique advantages over other proposed automated methods.

Amino Acid Sequence↗