title: Cyclization of a cell-penetrating peptide via click-chemistry increases proteolytic resistance and improves drug delivery.
abstract: In this work we report synthesis and biological evaluation of a cell-penetrating peptide (CPP), that is partly cyclized via a triazole bridge. Recently, beneficious properties have been reported for cyclized peptides concerning their metabolic stability and intracellular uptake. A CPP based on human calcitonin was used in this study, and side chain cyclization was achieved via copper catalyzed alkyne-azide click reaction. Cell viability studies in several cell-lines revealed no cytotoxic effects. Furthermore, efficient uptake in breast cancer MCF-7 cells could be determined. Moreover, preliminary studies using this novel peptide as drug transporter for daunorubicin were performed. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
authors.affiliation: Department of Chemistry, Institute of Biochemistry, University of Cologne, Zülpicher Str. 47, D-50674, Cologne, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Reichart
authors.affiliation: Department of Chemistry, Institute of Biochemistry, University of Cologne, Zülpicher Str. 47, D-50674, Cologne, Germany.
authors.forename: Mareike
authors.initials: M
authors.lastname: Horn
authors.affiliation: Department of Chemistry, Institute of Biochemistry, University of Cologne, Zülpicher Str. 47, D-50674, Cologne, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Neundorf
mesh_terms: D002116:Calcitonin / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D057930:Click Chemistry / Q000379:methods*; D003300:Copper / Q000737:chemistry; D003500:Cyclization; D003630:Daunorubicin / Q000494:pharmacology; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D059748:Proteolysis; D014230:Triazoles / Q000737:chemistry
chemical_list: D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D014230:Triazoles; D003300:Copper; D002116:Calcitonin; D003630:Daunorubicin
keywords: cell-penetrating peptides; click-reaction; drug delivery; peptide synthesis