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

• Published in: Advanced pharmaceutical bulletin 2015-06, Vol.5 (2), p.161-168
• Main Authors: Shirani, Ali, Shahbazi Mojarrad, Javid, Mussa Farkhani, Samad, yari khosroshahi, Ahmad, Zakeri-Milani, Parvin, Samadi, Naser, Sharifi, Simin, Mohammadi, Samaneh, Valizadeh, Hadi
• Format: Article
• Language: English
• Subjects: Cell-penetrating peptides (CPPs); GOR (Garnier-Osguthorpe- Robson) V method; Model amphipathic peptide (MAP); Wimley-White scale
• ISSN: 2228-5881; 2251-7308
• DOI: 10.15171/apb.2015.023

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.