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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Sequence length dependence in arginine/phenylalanine oligopeptides: Implications for self-assembly and cytotoxicity

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Author(s):
Silva, Emerson R. [1] ; Listik, Eduardo [2] ; Han, Sang W. [1] ; Alves, Wendel A. [3] ; Soares, Bruna M. [3] ; Reza, Mehedi [4] ; Ruokolainen, Janne [4] ; Hamley, Ian W. [5]
Total Authors: 8
Affiliation:
[1] Univ Fed Sao Paulo, Dept Biofis, Rua Botucatu 862, 7 Andar, BR-04023062 Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Ciencias Biomed, BR-05508900 Sao Paulo - Brazil
[3] Univ Fed ABC, Ctr Ciencias Nat & Humans, BR-09210580 Santo Andre - Brazil
[4] Aalto Univ, Dept Appl Phys, FI-00076 Aalto - Finland
[5] Univ Reading, Dept Chem, Reading RG6 6AD, Berks - England
Total Affiliations: 5
Document type: Journal article
Source: Biophysical Chemistry; v. 233, p. 1-12, FEB 2018.
Web of Science Citations: 7
Abstract

We present a detailed study on the self-assembly and cytotoxicity of arginine-rich fragments with general form {[}RF](n) (n = 1-5). These highly simplified sequences, containing only two L-amino acids, provide suitable models for exploring both structure and cytotoxicity features of arginine-based oligopeptides. The organization of the sequences is revealed over a range of length scales, from the nanometer range down to the level of molecular packing, and their cytotoxicity toward C6 rat glioma and RAW264.7 macrophage cell lines is investigated. We found that the polymorphism is dependent on peptide length, with a progressive increase in crystalline ordering upon increasing the number of {[}RF] pairs along the backbone. A dependence on length was also found for other observables, including critical aggregation concentrations, formation of chiral assemblies and half maximum inhibitory concentrations (IC50). Whereas shorter peptides self-assemble into fractal-like aggregates, clear fibrillogenic capabilities are identified for longer sequences with octameric and decameric chains exhibiting crystalline phases organized into cross-beta structures. Cell viability assays revealed dose-dependent cytotoxicity profiles with very similar behavior for both glioma and macrophage cell lines, which has been interpreted as evidence for a nonspecific mechanism involved in toxicity. We propose that structural organization of {[}RP](n) peptides plays a paramount role regarding toxicity due to strong increase of local charge density induced by self assemblies rich in cationic groups when interacting with cell membranes. (AU)

FAPESP's process: 16/24409-3 - Cell-Penetrating Peptides for Transport of Plasmid DNA and microRNA: from Nanoscopic Structure to Gene Delivery.
Grantee:Emerson Rodrigo da Silva
Support Opportunities: Regular Research Grants
FAPESP's process: 15/24018-1 - Polymer-Peptide Conjugates for hydrogel formulation and its usage in detection
Grantee:Wendel Andrade Alves
Support Opportunities: Regular Research Grants