No abstract

We describe here experiments designed to characterize the secondary structure of amyloid fibrils of the Alzheimer's amyloid plaque peptide A␤, using hydrogen-deuterium exchange measurements evaluated by mass spectrometry. The results show that Ϸ50% of the amide protons of the polypeptide backbone of A␤(1-40) resist exchange in aqueous, neutral pH buffer even after more than 1,000 h of incubation at room temperature. We attribute this extensive, strong protection to H-bonding by residues in core regions of ␤-sheet structure within the fibril. The backbone amide hydrogens exchange at variable rates, suggesting different degrees of protection within the fibril. These data suggest that it is unlikely that the entire A␤ sequence is involved in H-bonded secondary structure within the amyloid fibril. Future studies using the methods described here should reveal further details of A␤ fibril structure and assembly. These methods also should be amenable to studies of other amyloid fibrils and protein aggregates.

No abstract

The term "wrong-way-round ionization" has been used in studies of electrospray ionization to describe the observation of protonated or deprotonated ions when sampling strongly basic or acidic solutions (respectively) where such ions are not expected to exist in appreciable concentrations in solution. Study of the dependence of ionization of the weak base caffeine on the electrospray capillary potential reveals three distinct contributors to wrong-way-round ionization. At near-neutral pH in solutions of low ionic strength, protonation of caffeine results from the surface enrichment of electrolytically produced protons in the surface layer of the droplets from which ions are desorbed. For solutions made strongly basic with ammonia, gas-phase proton transfer from ammonium ions can create protonated caffeine. These two mechanisms have been discussed previously elsewhere. For solutions of high ionic strength at neutral or high pH, the data suggest that discharge-induced ionization is responsible for the production of protonated caffeine. This mechanism probably accounts for some of the wrong-way-round ionization reported elsewhere.