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Effects of N-terminal and C-terminal modification on cytotoxicity and cellular uptake of amphiphilic cell penetrating peptides

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posted on 2023-06-09, 09:39 authored by Mehdi Soleymani-Goloujeh, Ali Nokhodchi, Mehri Niazi, Saeedeh Najafi-Hajivar, Javid Shahbazi-Mojarrad, Nosratollah Zarghami, Parvin Zakeri-Milani, Ali Mohammadi, Mohammad Karimi, Hadi Valizadeh
Purpose: To assess the effect of “N-Acetylation and C-Amidation” on the cellular uptake, cytotoxicity and performance of amphiphilic Cell Penetrating Peptides loaded with MTX. Methods: Several CPPs were synthesized by solid phase peptide synthesis method. Some of these sequences were modified with Pyroglutamic acid at N-terminus and Benzylamine or memantine at C-terminus. The resultant nanomaterials were prepared due to the physical linkage between CPPs and methotrexate (MTX). The Internalization and cytotoxicity of both CPP-MTX bioconjugates and unmodified CPPs against MCF-7 cells was evaluated. Results: N-terminal and C-terminal modification did not alter the toxicity of CPPs. Physical linkage of CPPs with MTX resulted in a lower drug loading efficiency in comparison with chemically conjugated CPP-MTX bioconjugates. Both nanoparticles increase the toxic effect of MTX on MCF-7 cells. Furthermore, N-terminal and C-terminal modification may cause a tangible reduction in cellular uptake of CPPs. Conclusion: In conclusion, it was shown that cytotoxicity of modified peptides which were physically linked with MTX, considerably higher than both physically loaded unmodified peptides and chemically conjugated peptides with MTX. Also, cell internalization was reduced after peptide end-protection. These findings confirmed the effectiveness of N-terminal and C-terminal modifications on cell viability and CPPs internalization.

History

Publication status

  • Published

File Version

  • Accepted version

Journal

Artificial Cells, Nanomedicine, and Biotechnology

ISSN

2169-141x

Publisher

Informa Healthcare

Issue

sup1

Volume

46

Page range

91-103

Department affiliated with

  • Chemistry Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2018-01-08

First Open Access (FOA) Date

2018-12-19

First Compliant Deposit (FCD) Date

2018-01-08

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