title: The Relation Between Thermodynamic and Structural Properties and Cellular Uptake of Peptides Containing Tryptophan and Arginine.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Research Center for Pharmaceutical Nanotechnology and Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Shirani
authors.affiliation: Biotechnology Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Javid
authors.initials: J
authors.lastname: Shahbazi Mojarrad
authors.affiliation: Research Center for Pharmaceutical Nanotechnology and Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Samad
authors.initials: S
authors.lastname: Mussa Farkhani
authors.affiliation: Biotechnology Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Yari Khosroshahi
authors.affiliation: Liver and Gastrointestinal Diseases Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Parvin
authors.initials: P
authors.lastname: Zakeri-Milani
authors.affiliation: Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Naser
authors.initials: N
authors.lastname: Samadi
authors.affiliation: Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Simin
authors.initials: S
authors.lastname: Sharifi
authors.affiliation: Research Center for Pharmaceutical Nanotechnology and Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Samaneh
authors.initials: S
authors.lastname: Mohammadi
authors.affiliation: Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Hadi
authors.initials: H
authors.lastname: Valizadeh
keywords: Cell-penetrating peptides (CPPs); GOR (Garnier-Osguthorpe-Robson) V method; Model amphipathic peptide (MAP); Wimley-White scale