TY - JOUR
T1 - Principal component analysis of data from NMR titration experiment of uniformly 15N labeled amyloid beta (1–42) peptide with osmolytes and phenolic compounds
AU - Iwaya, Naoko
AU - Goda, Natsuko
AU - Matsuzaki, Mizuki
AU - Narita, Akihiro
AU - Shigemitsu, Yoshiki
AU - Tenno, Takeshi
AU - Abe, Yoshito
AU - Hoshi, Minako
AU - Hiroaki, Hidekazu
N1 - Funding Information:
Dr. K. Tomii (AIST) for help with the PCA method. The authors thank Dr. S. Matsumoto (Kyoto University) and Dr. Y. O. Kamatari (Gifu University) for help with the NMR measurements. This study was supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Sciences and Technology (Grant No. 21113007 ), Grants-in-Aid from the Japan Society for the Promotion of Science (Grant No. 16K14707 , 17H04055 ) and Grants-in-Aid for Nano Medicine (Grant No. H21-nano-007 ) from the Ministry of Health, Labor and Welfare . This work was supported by Salt Science Research Foundation (Grant No. 1222 ) and the Mishima Kaiun Memorial Foundation (Grant No. H25-153 ) in Japan.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/9/15
Y1 - 2020/9/15
N2 - A simple NMR method to analyze the data obtained by NMR titration experiment of amyloid formation inhibitors against uniformly 15N-labeled amyloid-β 1–42 peptide (Aβ(1–42)) was described. By using solution nuclear magnetic resonance (NMR) measurement, the simplest method for monitoring the effects of Aβ fibrilization inhibitors is the NMR chemical shift perturbation (CSP) experiment using 15N-labeled Aβ(1–42). However, the flexible and dynamic nature of Aβ(1–42) monomer may hamper the interpretation of CSP data. Here we introduced principal component analysis (PCA) for visualizing and analyzing NMR data of Aβ(1–42) in the presence of amyloid inhibitors including high concentration osmolytes. We measured 1H–15N 2D spectra of Aβ(1–42) at various temperatures as well as of Aβ(1–42) with several inhibitors, and subjected all the data to PCA (PCA-HSQC). The PCA diagram succeeded in differentiating the various amyloid inhibitors, including epigallocatechin gallate (EGCg), rosmarinic acid (RA) and curcumin (CUR) from high concentration osmolytes. We hypothesized that the CSPs reflected the conformational equilibrium of intrinsically disordered Aβ(1–42) induced by weak inhibitor binding rather than the specific molecular interactions.
AB - A simple NMR method to analyze the data obtained by NMR titration experiment of amyloid formation inhibitors against uniformly 15N-labeled amyloid-β 1–42 peptide (Aβ(1–42)) was described. By using solution nuclear magnetic resonance (NMR) measurement, the simplest method for monitoring the effects of Aβ fibrilization inhibitors is the NMR chemical shift perturbation (CSP) experiment using 15N-labeled Aβ(1–42). However, the flexible and dynamic nature of Aβ(1–42) monomer may hamper the interpretation of CSP data. Here we introduced principal component analysis (PCA) for visualizing and analyzing NMR data of Aβ(1–42) in the presence of amyloid inhibitors including high concentration osmolytes. We measured 1H–15N 2D spectra of Aβ(1–42) at various temperatures as well as of Aβ(1–42) with several inhibitors, and subjected all the data to PCA (PCA-HSQC). The PCA diagram succeeded in differentiating the various amyloid inhibitors, including epigallocatechin gallate (EGCg), rosmarinic acid (RA) and curcumin (CUR) from high concentration osmolytes. We hypothesized that the CSPs reflected the conformational equilibrium of intrinsically disordered Aβ(1–42) induced by weak inhibitor binding rather than the specific molecular interactions.
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U2 - 10.1016/j.abb.2020.108446
DO - 10.1016/j.abb.2020.108446
M3 - Article
C2 - 32593678
AN - SCOPUS:85087514277
VL - 690
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
SN - 0003-9861
M1 - 108446
ER -