title: Introducing PeptoPlexes: polylysine-block-polysarcosine based polyplexes for transfection of HEK 293T cells.
abstract: A series of well-defined polypeptide-polypeptoid block copolymers based on the body's own amino acids sarcosine and lysine are prepared by ring opening polymerization of N-carboxyanhydrides. Block lengths were varied between 200-300 for the shielding polysarcosine block and 20-70 for the complexing polylysine block. Dispersity indexes ranged from 1.05 to 1.18. Polylysine is polymerized with benzyloxycarbonyl as well as trifluoroacetyl protecting groups at the ϵ-amine group and optimized deprotection protocols for both groups are reported. The obtained block ionomers are used to complex pDNA resulting in the formation of polyplexes (PeptoPlexes). The PeptoPlexes can be successfully applied in the transfection of HEK 293T cells and are able to transfect up to 50% of cells in vitro (FACS assay), while causing no detectable toxicity in an Annexin V assay. These findings are a first indication that PeptoPlexes may be a suitable alternative to PEG based non-viral transfection systems.
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, D-55128, Mainz, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Heller
authors.forename: Alexander
authors.initials: A
authors.lastname: Birke
authors.forename: David
authors.initials: D
authors.lastname: Huesmann
authors.forename: Benjamin
authors.initials: B
authors.lastname: Weber
authors.forename: Karl
authors.initials: K
authors.lastname: Fischer
authors.forename: Angelika
authors.initials: A
authors.lastname: Reske-Kunz
authors.forename: Matthias
authors.initials: M
authors.lastname: Bros
authors.forename: Matthias
authors.initials: M
authors.lastname: Barz
mesh_terms: D000812:Anhydrides / Q000737:chemistry; D017304:Annexin A5; D002470:Cell Survival; D004247:DNA / Q000737:chemistry*; D005456:Fluorescent Dyes; D057809:HEK293 Cells; D006801:Humans; D010455:Peptides / Q000737:chemistry*; D010957:Plasmids / Q000737:chemistry*; D011107:Polylysine / Q000737:chemistry*; D058105:Polymerization; D012521:Sarcosine / Q000031:analogs & derivatives* / Q000737:chemistry; D014162:Transfection / Q000379:methods*
chemical_list: D000812:Anhydrides; D017304:Annexin A5; D005456:Fluorescent Dyes; D010455:Peptides; D011107:Polylysine; C015475:polysarcosine; D004247:DNA; D012521:Sarcosine
keywords: cytotoxicity; non-viral gene delivery; polylysine; polysarcosine