title: The Plasma Membrane as a Reservoir, Protective Shield, and Light-Triggered Launch Pad for Peptide Therapeutics.
abstract: Although peptide-based therapeutics are finding increasing application in the clinic, extensive structural modification is typically required to prevent their rapid degradation by proteases in the blood. We have evaluated the ability of erythrocytes to serve as reservoirs, protective shields (against proteases), and light-triggered launch pads for peptides. We designed lipidated peptides that are anchored to the surface of red blood cells, which furnishes a protease-resistant environment. A photocleavable moiety is inserted between the lipid anchor and the peptide backbone, thereby enabling light-triggered peptide release from erythrocytes. We have shown that a cell-permeable peptide, a hormone (melanocyte stimulating hormone), and a blood-clotting agent can be anchored to erythrocytes, protected from proteases, and photolytically released to create the desired biological effect.
authors.affiliation: Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, and Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors.forename: Colin P
authors.initials: CP
authors.lastname: O'Banion
authors.affiliation: Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, and Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors.forename: Luong T
authors.initials: LT
authors.lastname: Nguyen
authors.affiliation: Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, and Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors.forename: Qunzhao
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, and Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Priestman
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Holly
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors.forename: Leslie V
authors.initials: LV
authors.lastname: Parise
authors.affiliation: Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, and Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 27599, USA. lawrencd@email.unc.edu.
authors.forename: David S
authors.initials: DS
authors.lastname: Lawrence
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D008565:Membrane Proteins; D010455:Peptides
keywords: peptide drugs; peptides; photochemistry; proteolysis; targeted delivery