title: Cysteine and arginine-rich peptides as molecular carriers.
abstract: A number of linear and cyclic peptides containing alternative arginine and cysteine residues, namely linear (CR)3, linear (CR)4, linear (CR)5, cyclic [CR]4, and cyclic [CR]5, were synthesized. The peptides were evaluated for their ability to deliver two molecular cargos, fluorescence-labeled cell-impermeable negatively charged phosphopeptide (F'-GpYEEI) and fluorescence-labeled lamivudine (F'-3TC), intracellularly in human leukemia cancer (CCRF-CEM) cells. We investigated the role of cyclization and the number of amino acids in improving the transporting ability of the peptides. The flow cytometry studies suggested that the synthesized peptides were able to work efficiently as transporters for both cargos. Among all compounds, cyclic [CR]4 was found to be the most efficient peptide in transporting the cargo into cells. For instance, the cellular uptake of F'-3TC (5μM) and F'-GpYEEI (5μM) was enhanced by 16- and 20-fold, respectively, in the presence of cyclic [CR]4 compared to that of the parent compound alone. The mechanism of F'-GpYEEI uptake by cells was found to be energy-independent. The results showed that the number of amino acids and their cyclic nature can impact the efficiency of the peptide in transporting the molecular cargos.
authors.affiliation: Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, Irvine, CA 92618, United States.
authors.forename: Amir Nasrolahi
authors.initials: AN
authors.lastname: Shirazi
authors.affiliation: Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, Irvine, CA 92618, United States.
authors.forename: Naglaa Salem
authors.initials: NS
authors.lastname: El-Sayed
authors.affiliation: Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, Irvine, CA 92618, United States.
authors.forename: Dindayal
authors.initials: D
authors.lastname: Mandal
authors.affiliation: Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, Irvine, CA 92618, United States.
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Tiwari
authors.affiliation: Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, Irvine, CA 92618, United States.
authors.forename: Kathy
authors.initials: K
authors.lastname: Tavakoli
authors.affiliation: Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, Irvine, CA 92618, United States.
authors.forename: Matthew
authors.initials: M
authors.lastname: Etesham
authors.affiliation: Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, Irvine, CA 92618, United States. Electronic address: parang@chapman.edu.
authors.forename: Keykavous
authors.initials: K
authors.lastname: Parang
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001120:Arginine / Q000737:chemistry*; D045744:Cell Line, Tumor; D003545:Cysteine / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000493:pharmacokinetics; D010455:Peptides / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry; D010748:Phosphopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D019380:Anti-HIV Agents; D004337:Drug Carriers; D010455:Peptides; D010456:Peptides, Cyclic; D010748:Phosphopeptides; D019259:Lamivudine; D001120:Arginine; D003545:Cysteine
keywords: Arginine; Cysteine; Drug delivery; Formulation; Peptide