Refinement of the crystal structure of (RS)-carnitine hydrochloride

A single crystal of (RS)-carnitine hydrochloride has been obtained, and its crystal structure has been refined by an x-ray structural experiment.Tashkent Pharmaceutical Institute. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 842–844, November–December, 1991.     

Utilizing Lifetimes to Suppress Random Coil Features in 2D IR Spectra of Peptides

We report that the waiting time delay in 2D IR pulse sequences can be used to suppress signals from structurally disordered regions of amyloid fibrils. At a waiting time delay of 1.0 ps, the random coil vibrational modes of amylin fibrils are no longer detectable, leaving only the sharp excitonic vibrational features of the fibril β-sheets. Isotope labeling with (13)C(18)O reveals that structurally disordered residues decay faster than residues protected from solvent. Since structural disorder is usually accompanied by hydration, we conclude that the shorter lifetimes of random-coil residues is due to solvent exposure. These results indicate that 2D IR pulse sequences can utilize the waiting time to better resolve solvent-protected regions of peptides and that local mode lifetimes should be included in simulations of 2D IR spectra.     

Deamidation accelerates amyloid formation and alters amylin fiber structure

Deamidation of asparagine and glutamine is the most common nonenzymatic, post-translational modification. Deamidation can influence the structure, stability, folding, and aggregation of proteins and has been proposed to play a role in amyloid formation. However there are no structural studies of the consequences of deamidation on amyloid fibers, in large part because of the difficulty of studying these materials using conventional methods. Here we examine the effects of deamidation on the kinetics of amyloid formation by amylin, the causative agent of type 2 diabetes. We find that deamidation accelerates amyloid formation and the deamidated material is able to seed amyloid formation by unmodified amylin. Using site-specific isotope labeling and two-dimensional infrared (2D IR) spectroscopy, we show that fibers formed by samples that contain deamidated polypeptide contain reduced amounts of β-sheet. Deamidation leads to disruption of the N-terminal β-sheet between Ala-8 and Ala-13, but β-sheet is still retained near Leu-16. The C-terminal sheet is disrupted near Leu-27. Analysis of potential sites of deamidation together with structural models of amylin fibers reveals that deamidation in the N-terminal β-sheet region may be the cause for the disruption of the fiber structure at both the N- and C-terminal β-sheet. Thus, deamidation is a post-translational modification that creates fibers that have an altered structure but can still act as a template for amylin aggregation. Deamidation is very difficult to detect with standard methods used to follow amyloid formation, but isotope-labeled IR spectroscopy provides a means for monitoring sample degradation and investigating the structural consequences of deamidation.     

Refinement of the crystal structure of (RS)-carnitine hydrochloride

A single crystal of (RS)-carnitine hydrochloride has been obtained, and its crystal structure has been refined by an x-ray structural experiment.     

Photoisomerization and relaxation dynamics of a structurally modified biomimetic photoswitch

Recent experimental and theoretical studies on N-alkylated indanylidene pyrroline Schiff bases (NAIP) show that these compounds exhibit biomimetic photoisomerization analogous to that in the chromophore of rhodopsin. The NAIP compounds studied previously isomerize rapidly and often evolve coherently on the ground-electronic surface after reaction. We present the results of transient electronic absorption spectroscopy on dMe-OMe-NAIP, a newly synthesized NAIP analogue that differs from other NAIP compounds in the substituents on its pyrrolinium ring. Following excitation with 400 nm light, dMe-OMe-NAIP relaxes from the electronic-excited state in less than 500 fs, which is slower than in other analogues, and does not show the prominent oscillations observed in other NAIP compounds. A reduction in the amount of twisting between the rings caused by removal of the methyl group is likely responsible for the slower isomerization. Measurements in solvents of varying viscosity and structure suggest that intramolecular processes dominate the relaxation of nascent photoproducts.