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pH-Dependent In-Cell Self-Assembly of Peptide Inhibitors Increases the Anti-Prion Activity While Decreasing the Cytotoxicity

Title
pH-Dependent In-Cell Self-Assembly of Peptide Inhibitors Increases the Anti-Prion Activity While Decreasing the Cytotoxicity
Author
류종석
Keywords
DESIGN; MOLECULES; NEURODEGENERATIVE DIEASSE; PENETRATING PEPTIDES; BRANCHED POLYAMINES; PROTEIN; AGGREGATION; ALZHEIMERS; DELIVERY
Issue Date
2017-01
Publisher
AMER CHEMICAL SOC
Citation
BIOMACROMOLECULES, v. 18, No. 3, Page. 943-950
Abstract
The first step in the conventional approach to self-assembled biomaterials is to develop well-defined nano structures in vitro, which is followed by disruption of the preformed nanostructures at the inside of the cell to achieve bioactivity. Here, we propose an inverse strategy to develop in-cell gain-of-function self-assembled nanostructures. In this approach, the supramolecular building blocks exist in a unimolecular/unordered state in vitro or at the outside of the cell and assemble into well-defined nanostructures after cell internalization. We used block copolypeptides of an oligoarginine and a self-assembling peptide as building blocks and investigated correlations among the nanostructural state, antiprion bioactivity, and cytotoxicity. The optimal bioactivity (i.e., the highest antiprion activity and lowest cytotoxicity) was obtained when the building blocks existed In a unimolecular/unordered state in vitro and during the cell internalization process, exerting minimal cytotoxic damage to cell membranes, and were subsequently converted into high-charge-density vesicles in the low pH endosome/lysosomes in vivo, thus, resulting in the significantly enhanced antiprion activity. In particular, the in-cell self assembly concept presents a feasible approach to developing therapeutics against protein misfolding diseases. In general, the in cell self-assembly provides a novel inverse methodology to supramolecular bionanomaterials.
URI
https://pubs.acs.org/doi/abs/10.1021/acs.biomac.6b01816http://repository.hanyang.ac.kr/handle/20.500.11754/103089
ISSN
1526-4602; 1525-7797
DOI
10.1021/acs.biomac.6b01816
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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