Effects of N-Terminal Residues on the Assembly of Constrained ß-Hairpin Peptides Derived from Aß.

This paper describes the synthesis, solution-phase biophysical studies, and X-ray crystallographic structures of hexamers formed by macrocyclic ß-hairpin peptides derived from the central and C-terminal regions of Aß, which bear "tails" derived from the N-terminus of Aß. Soluble oligomers of the ß-amyloid peptide, Aß, are thought to be the synaptotoxic species responsible for neurodegeneration in Alzheimer's disease. Over the last 20 years, evidence has accumulated that implicates the N-terminus of Aß as a region that may initiate the formation of damaging oligomeric species. We previously studied, in our laboratory, macrocyclic ß-hairpin peptides derived from Aß16-22 and Aß30-36, capable of forming hexamers that can be observed by X-ray crystallography and SDS-PAGE. To better mimic oligomers of full length Aß, we use an orthogonal protecting group strategy during the synthesis to append residues from Aß1-14 to the parent macrocyclic ß-hairpin peptide 1, which comprises Aß16-22 and Aß30-36. The N-terminally extended peptides N+1, N+2, N+4, N+6, N+8, N+10, N+12, and N+14 assemble to form dimers, trimers, and hexamers in solution-phase studies. X-ray crystallography reveals that peptide N+1 assembles to form a hexamer that is composed of dimers and trimers. These observations are consistent with a model in which the assembly of Aß oligomers is driven by hydrogen bonding and hydrophobic packing of the residues from the central and C-terminal regions, with the N-terminus of Aß accommodated by the oligomers as an unstructured tail.

Assessing the Oxidative Degradation of N-Methylpyrrolidone (NMP) in Microelectronic Fabrication Processes by Using a Multiplatform Analytical Approach.

During the construction of recording head devices, corrosion of metal features and subsequent deposition of corrosion by-products have been observed. Previous studies have determined that the use of N-methylpyrrolidone (NMP) may be a contributing factor. In this study, we report the use of a novel multiplatform analytical approach comprising of pH, liquid chromatography/UV detection (LC/UV), inductively coupled plasma optical emission spectroscopy (ICP-OES), and LC/mass spectrometry (LC/MS) to demonstrate that reaction conditions mimicking those of general photoresist removal processes can invoke the oxidation of NMP during the photolithography lift-off process. For the first time, we have confirmed that the oxidation of NMP lowers the pH, facilitating the dissolution of transition metals deposited on wafer substrates during post-mask and pre-lift-off processes in microelectronic fabrication. This negatively impacts upon the performance of the microelectronic device. Furthermore, it was shown that, by performing the process in an inert atmosphere, the oxidation of NMP was suppressed and the pH was stabilized, suggesting an affordable modification of the photolithography lift-off stage to enhance the quality of recording heads. This novel study has provided key data that may have a significant impact on current and future fabrication process design, optimization, and control. Results here suggest the inclusion of pH as a key process input variable (KPIV) during the design of new photoresist removal processes.