Pyrene conjugation and spectroscopic analysis of hydroxypropyl methylcellulose compounds successfully demonstrated a local dielectric difference associated with in vivo anti-prion activity.

Kenta Teruya,Keiko Nishizawa,Katsumi Doh-Ura,Hiroshi Kamitakahara,Ayumi Oguma,Byron Caughey

doi:10.1371/journal.pone.0185357

Kenta Teruya, Keiko Nishizawa + Show 4 more

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https://doi.org/10.1371/journal.pone.0185357

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Journal: PloS one	Publication Date: Sep 21, 2017
Citations: 10	License type: CC BY 4.0

Affiliation: Tohoku University, Kyoto University

Abstract

Our previous study on prion-infected rodents revealed that hydroxypropyl methylcellulose compounds (HPMCs) with different molecular weights but similar composition and degree of substitution have different levels of long-lasting anti-prion activity. In this study, we searched these HPMCs for a parameter specifically associated with in vivo anti-prion activity by analyzing in vitro chemical properties and in vivo tissue distributions. Infrared spectroscopic and thermal analyses revealed no differences among HPMCs, whereas pyrene conjugation and spectroscopic analysis revealed that the fluorescence intensity ratio of peak III/peak I correlated with anti-prion activity. This correlation was more clearly demonstrated in the anti-prion activity of the 1-year pre-infection treatment than that of the immediate post-infection treatment. In addition, the intensity ratio of peak III/peak I negatively correlated with the macrophage uptake level of HPMCs in our previous study. However, the in vivo distribution pattern was apparently not associated with anti-prion activity and was different in the representative tissues. These findings suggest that pyrene conjugation and spectroscopic analysis are powerful methods to successfully demonstrate local dielectric differences in HPMCs and provide a feasible parameter denoting the long-lasting anti-prion activity of HPMCs in vivo.

Highlights

Prion diseases, including Creutzfeldt–Jakob disease in humans, are progressive fatal neurodegenerative illnesses [1] characterized by the pathogenic accumulation of abnormal prion proteins, which are the primary components of the infectious agent called a prion
The properties of hydroxypropyl methylcellulose compounds (HPMCs) are characterized by their molar degree of substitution on the anhydroglucose unit and the degree of polymerization corresponding to Mn
The experimental conditions were different, the observed HPMC transition temperatures in this study were consistent with those reported previously [23]. These results clearly indicate that the thermal analysis cannot detect any parameters linked to in vivo anti-prion activities; net interactions with the solvent were similar among HPMCs with a similar composition and degree of substitution, which is consistent with the interpretation of the matched intensity of the 1640 cm−1 band among the HPMCs in the Fourier-transform infrared spectroscopy (FTIR) analysis

Summary

Introduction

Prion diseases, including Creutzfeldt–Jakob disease in humans, are progressive fatal neurodegenerative illnesses [1] characterized by the pathogenic accumulation of abnormal prion proteins, which are the primary components of the infectious agent called a prion. Prions conformationally transform normal proteins into abnormal proteins in the central nervous. Pyrene index of HPMC with anti-prion activity. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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