Adv Pharm Bull. 2015;5(2):161-168.
doi: 10.15171/apb.2015.023
PMID: 26236653
PMCID: PMC4517088
Scopus id: 84930393567
  Abstract View: 347
  PDF Download: 170

Original Research

The Relation Between Thermodynamic and Structural Properties and Cellular Uptake of Peptides Containing Tryptophan and Arginine

Ali Shirani 1, Javid Shahbazi Mojarrad 2, Samad Mussa Farkhani 1, Ahmad yari khosroshahi 2, Parvin Zakeri-Milani 3, Naser Samadi 4, Simin Sharifi 5, Samaneh Mohammadi 1, Hadi Valizadeh 5 *

1 Research Center for Pharmaceutical Nanotechnology and Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
2 Biotechnology Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
3 Liver and Gastrointestinal Diseases Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
4 Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
5 Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.

Abstract

Purpose: Cell-penetrating peptides (CPPs) are used for delivering drugs and other macromolecular cargo into living cells. In this paper, we investigated the relationship between the structural/physicochemical properties of four new synthetic peptides containing arginine-tryptophan in terms of their cell membrane penetration efficiency. Methods: The peptides were prepared using solid phase synthesis procedure using FMOC protected amino acids. Fluorescence-activated cell sorting and fluorescence imaging were used to evaluate uptake efficiency. Prediction of the peptide secondary structure and estimation of physicochemical properties was performed using the GOR V method and MPEx 3.2 software (Wimley-White scale, helical wheel projection and total hydrophobic moment). Results: Our data showed that the uptake efficiency of peptides with two tryptophans at the C- and N-terminus were significantly higher (about 4-fold) than that of peptides containing three tryptophans at both ends. The distribution of arginine at both ends also increased the uptake efficiency 2.52- and 7.18-fold, compared with arginine distribution at the middle of peptides. Conclusion: According to the obtained results the value of transfer free energies of peptides from the aqueous phase to membrane bilayer could be a good predictor for the cellular uptake efficiency of CPPs.
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