Human islet amyloid polypeptide (hIAPP) forms cytotoxic fibrils in type-2 diabetes and insulin is known to inhibit formation of these aggregates. In this study, a series of insulin-based inhibitors were synthesized and assessed for their ability to slow aggregation and impact hIAPP-induced membrane damage. Computational studies were employed to examine the underlying mechanism of inhibition. Overall, all compounds were able to slow aggregation at sufficiently high concentrations (10× molar excess); however, only two peptides showed any inhibitory capability at the 1:1 molar ratio (EALYLV and VEALYLV). The results of density functional calculations suggest this is due to the strength of a salt bridge formed with the Arg11 side chain of hIAPP and the inhibitors' ability to span from the Arg11 to past the Phe15 residue of hIAPP, blocking one of the principal amyloidogenic regions of the molecule. Unexpectedly, slowing fibrillogenesis actually increased damage to lipid membranes, suggesting that the aggregation process itself, rather than the fibrilized peptide, may be the cause of cytotoxicity in vivo.
The complex and colorful textiles of ancient Peru have long been a focus of technical study, particularly to characterize the sources of the wide variety of dyes utilized by these Andean artisans. This manuscript describes the characterization of the dyes of both primary (red, blue, and yellow) and secondary (purple, orange, and green) colors sampled from textiles spanning five major civilizations: the Paracas Necropolis, the Nazca, the Wari, the Chancay, and the Lambayeque, all from Peru. All but the Paracas Necropolis samples were part of technical conservation studies of the ancient South American textiles collections of the Michael C. Carlos Museum. Analysis of the dyes was carried out utilizing direct analysis in real time time-of-flight mass spectrometry (DART-MS) and paper spray MS. To validate these ambient ionization MS methods, the samples were further investigated using high-performance liquid chromatography (HPLC) with ultraviolet-visible diode array detection (DAD). These results show that ambient ionization MS methods are simple and fast for characterization of the general classes of dyes, e.g., plant reds vs. insect reds, and indigoids in blues and greens. Due to the myriad possible sources of yellow dyes and their tendency to undergo oxidative decomposition, positively identifying those components in these yarns was difficult, though some marker compounds and flavonoid decomposition products were readily identified by ambient ionization mass spectrometry.
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