title: Flow and Microwave-Assisted Synthesis of N-(Triethylene glycol)glycine Oligomers and Their Remarkable Cellular Transporter Activities.
abstract: Peptidomimetics, such as oligo-N-alkylglycines (peptoids), are attractive alternatives to traditional cationic cell-penetrating peptides (such as R9) due to their robust proteolytic stability and reduced cellular toxicity. Here, monomeric N-alkylglycines, incorporating amino-functionalized hexyl or triethylene glycol (TEG) side chains, were synthesized via a three-step continuous-flow reaction sequence, giving the monomers N-Fmoc-(6-Boc-aminohexyl)glycine and N-Fmoc-((2-(2-Boc-aminoethoxy)ethoxy)ethyl)glycine in 49% and 41% overall yields, respectively. These were converted into oligomers (5, 7, and 9-mers) using an Fmoc-based solid-phase protocol and evaluated as cellular transporters. Hybrid oligomers, constructed of alternating units of the aminohexyl and amino-TEG monomers, were non-cytotoxic and exhibited remarkable cellular uptake activity compared to the analogous fully TEG or lysine-like compounds.
authors.affiliation: School of Chemistry, EaStCHEM, University of Edinburgh, Joseph Black Building, King's Buildings, West Mains Road, EH9 3FJ Edinburgh, United Kingdom.
authors.forename: ThingSoon
authors.initials: T
authors.lastname: Jong
authors.affiliation: School of Chemistry, EaStCHEM, University of Edinburgh, Joseph Black Building, King's Buildings, West Mains Road, EH9 3FJ Edinburgh, United Kingdom.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Pérez-López
authors.affiliation: School of Chemistry, EaStCHEM, University of Edinburgh, Joseph Black Building, King's Buildings, West Mains Road, EH9 3FJ Edinburgh, United Kingdom.
authors.forename: Emma M V
authors.initials: EM
authors.lastname: Johansson
authors.affiliation: School of Chemistry, EaStCHEM, University of Edinburgh, Joseph Black Building, King's Buildings, West Mains Road, EH9 3FJ Edinburgh, United Kingdom.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Lilienkampf
authors.affiliation: School of Chemistry, EaStCHEM, University of Edinburgh, Joseph Black Building, King's Buildings, West Mains Road, EH9 3FJ Edinburgh, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Bradley
mesh_terms: D001692:Biological Transport; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000493:pharmacokinetics; D002478:Cells, Cultured; D015195:Drug Design; D005998:Glycine / Q000737:chemistry*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008239:Lysine / Q000737:chemistry*; D008872:Microwaves; D057786:Peptidomimetics / Q000737:chemistry; D034444:Peptoids / Q000737:chemistry* / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D057846:Cell-Penetrating Peptides; D057786:Peptidomimetics; D034444:Peptoids; C028914:triethylene glycol; D011092:Polyethylene Glycols; D008239:Lysine; D005998:Glycine