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

Soleymani-Goloujeh, Mehdi, Nokhodchi, Ali, Niazi, Mehri, Najafi-Hajivar, Saeedeh, Shahbazi-Mojarrad, Javid, Zarghami, Nosratollah, Zakeri-Milani, Parvin, Mohammadi, Ali, Karimi, Mohammad and Valizadeh, Hadi (2018) Effects of N-terminal and C-terminal modification on cytotoxicity and cellular uptake of amphiphilic cell penetrating peptides. Artificial Cells, Nanomedicine, and Biotechnology, 46 (sup1). pp. 91-103. ISSN 2169-141x

[img] PDF - Accepted Version
Download (1MB)


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.

Item Type: Article
Schools and Departments: School of Life Sciences > Chemistry
Subjects: R Medicine > RS Pharmacy and materia medica > RS0153 Materia medica > RS0192 Pharmaceutical technology
Depositing User: Ali Nokhodchi
Date Deposited: 08 Jan 2018 11:19
Last Modified: 01 Jul 2019 16:19
URI: http://sro.sussex.ac.uk/id/eprint/72659

View download statistics for this item

📧 Request an update