Fragment capture principles

At the time of this writing, it must be conceded that there have been no fundamental principles-based mathematical model for Nafion that has predicted significantly new phenomena or caused property improvements in a significant way. Models that capture the essence of percolation behavior ignore chemical identity. The more ab initio methods that do embrace chemical structure are limited by the number of molecular fragments that the computer can accommodate. Other models are semiempirical in nature, which limits their predictive flexibility. Nonetheless, the diversity of these interesting approaches offers structural perspectives that can serve as guides toward further experimental inquiry. 

Similar concerns regarding the stability of our activated lipid intermediate led us to reject a method that involves the in situ preparation of lipid-derived phosphoric anhydrides.22 The common theme for each of the methods illustrated above is that each involves activation of the lipid intermediate for the diphosphate coupling reaction. Given the expense of the undecaprenyl monophosphate precursor, we sought a method that would entail activation of the carbohydrate fragment for capture by an undecaprenyl monophosphate nucleophile. This, in principle, would also allow the opportunity for the coupling reaction to take place under basic reaction conditions and enable us to preserve the chemical integrity of our expensive lipid precursor. 

Figure 10.1 Principle of covalent capture methods. Drug fragments typically have weak binding affinity and can therefore be difficult to detect. By introducing two reactive groups, X and Y, a fragment that binds in the vicinity of X can be captured covalently by the protein target and easily identified by mass spectrometry.

Template-mediated ligation, an approach to bring two peptide fragments into close proximity. The N-terminus of one peptide and C-terminus of the other peptide are attached to a template, and consequently close to each other so that they can form a peptide bond. The basic principle was created by Brenner et al. using a salicylamide template based on a base-catalyzed intramolecular rearrangement and has been later exploited in thiol capture ligation [M. Bretmer et al., Helv. Chim. Acta 1957, 40, 1497]. 

Chapter 5 provides an overview of Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry and its applications in the structural characterization of peptides and proteins. The principles of FT-ICR, that is, ion motion, ion excitation/ detection, and instrumental considerations, are discussed and an explanation of the features of FT-ICR that make it so suitable for peptide/protein analysis is presented. New methods for the fragmentation of peptide and protein ions in FT-ICR mass spectrometry, such as sustained off-resonance irradiation collision-induced dissociation (SORI-CID), infrared multiphoton dissociation (IRMPD), blackbody infrared radiative dissociation (BIRD), surface-induced dissociation (SID), and electron capture dissociation (BCD), are described in detail. Innovative hybrid FT-ICR instruments, which have recently become available, are reviewed. In conclusion, the chapter discusses the applications of FT-ICR in bottom-up and top-down proteomics. 

True Np Activity. To determine the magnitude of the contribution of fission product activity to the Np peak, the special foil package of Fig. 12.5 is included for the irradiation. The enriched uranium metal foil is a source of recoil fission fragments which are captured by the aluminum catcher foil. In principle, the source uranium foil (1.46 a/o should... 

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