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1、Report: Two-dimensional infrared spectra of isotopically diluted amyloid fibrils from A40 Two-dimensional infrared spectra(2DIR) is a nonlinear infrared spectroscopy which has the ability to correlate vibrational modes. This technique can provides detailed information beyond linear infrared spectros
2、copy by spreading the vibrational information along multiple axes. The 2DIR spectrum can offer structure information about vibrational coupling, anharmonicities and chemical dynamics. Normally a 2DIR spectroscopy involves three beams. The first beam is to excite the molecule from its ground vibratio
3、nal state to its first vibrational state. The second beam is to excite the molecule from its first vibrational state to its second vibrational state. And a third beam is to probe the radiation from the excited molecule. Then a fouth beam is observed on a detector. Compared with 2D NMR, IR pulse sequ
4、ence has a higher sensitivity to dynamics on time scales 6-10 orders of magnitude faster than NMR pulse sequence.This paper utilize 2DIR to detect amyloid fibril from A40. Amyloid fibrils are found in the brain tissue of persons with Alzheimers disease, where they accumulate as plaques surrounded by
5、 regions of neuronal death. Although it is still remaining unclear that whether amyloids fibrils are related to the neuronal loss in Alzheimers disease, the formation and structure of amyloid fibril is interesting researchers. Amyloid-beta denotes peptides of 36-43 amino acids. This paper mainly tal
6、k about A40. And they use 13C=18O substitute 12C=16O at Gly-38, Gly-33, Gly-29 and Gly-25. As the picture shows, A40 is beta sheet which has Gly-25 on the corner and Gly-38, Gly-33, Gly-29 distributed along a line.A40 IR spectra are dominated by motions in backbone C=O groups, but they are strongly
7、influenced by intrastrand coupling. When an amyloid fibril is formed from A40, the substituted 13C=18O group could form a linear array along the fibril axis. At the same time, the interaction magnitude of unsubstituted group is reduced by the ratio of coupling to the isotope shift. In this paper, th
8、ey tried two different solution of the A40. One is pure 13C=18O substituted A40, and the other is a 1:1 mixture of 13C=18O and 12C=16O. The signals of both solution look the similar, but pure substituted groups have a bigger amplitude. They tried to detect the whole fibril formation process. So they
9、 do the experiment at different maturation times, as 6 days, 12 days and 19 days. The result is at earlier maturation times, in solutions before fibril formed, the maxima are in the region of 1645-1650 cm-1 and the peaks are decreasing from day 6 to day 12. Which indicate that a homogeneous fibril i
10、s forming during this period. After day 12, the peaks did not change very much. The paper also plot the experimental and simulated traces of A40. We could see the main peak of mixed solution has a shift from the pure substituted solution. The 13C=18O 2DIR peak is at 1586.5 cm-1 and split by 9 cm-1.
11、And 12C=16O peak is mainly at 1625 cm-1. From the signal change of different times, we could conclude the 12C=16O are less sensitive to maturation than 13C=18O, because the 13C=18O signal has a considerably big change compared with the same 12C=16O peak at different maturation time. They also compar
12、ed the G25 with G29. As illustrated before, G25 is at the corner of the sheet while G29 is at the strand of the sheet. There is a crossing peak at G29 result, which indicates there exists mode and mode coupling. And results also show that the signal amplitude of G25 signal is only about 12% of ampli
13、tude observed from other isotopomers. And this really matches what the amyloid fibril structure is. Except the 2DIR part of the amyloid fibril, they also checked the formation of amyloid fibril at two different pD. When they use low pD(pD=2), the rate of formation is very low. And long straight fibrils are formed, which resembles those found in diseased brain tissue. At pD 7.4, the fibrils are formed short and curvilinear.
