title: Peptide-Mediated PEGylation of Polysulfone Reduces Protein Adsorption and Leukocyte Activation.
abstract: The exposure of blood to bioincompatible materials used for dialysis triggers leukocyte activation and protein adsorption. We describe a single-step, postmanufacturing method for surface modification to create biomaterials used in medical devices and dialysis with altered surface characteristics. Peptides derived from the receptor-binding domain of the type IV pilin of Pseudomonas aeruginosa were synthesized using L and D-amino acids to generate L-K122-4, enantiomer D-K122-4, and D-retroinverso RI-K122-4 peptides. L-K122-4, D-K122-4, and RI-K122-4 peptides, but not control peptides, bound durably to the surfaces of materials used in medical devices and dialysis including silicone and polysulfone. D-K122-4 enantiomeric peptides were protease resistant on polysulfone and could remain bound to the surface for up to 28 days. To demonstrate that K122-4 peptides could be used to modify material surfaces, D-K122-4 peptide was conjugated to polyethylene glycol (D-K122-4-PEG) and applied to polysulfone. When compared with untreated material, D-K122-4-PEG reduced the surface adsorption of albumin or immunoglobulin G to polysulfone. In coincubation experiments, although uncoated polysulfone induced pro-interleukin-1β cytokine expression in leukocytes, cellular activation was prevented when leukocytes were incubated with D-K122-4-PEG-modified polysulfone. These data demonstrate the proof of principle that K122-4 peptides can be applied to modify the surface characteristics of materials used for dialysis.
authors.affiliation: From the *Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta; and †Department of Medicine, University of Calgary, Calgary, Alberta, Canada. Dr. Davis is currently at University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Davis
authors.forename: Jaye M
authors.initials: JM
authors.lastname: Platnich
authors.forename: Randall T
authors.initials: RT
authors.lastname: Irvin
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Muruve
mesh_terms: D000327:Adsorption / Q000187:drug effects*; D020099:Coated Materials, Biocompatible; D036781:Fimbriae Proteins / Q000008:administration & dosage* / Q000502:physiology; D010861:Fimbriae, Bacterial / Q000502:physiology; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D008567:Membranes, Artificial; D010455:Peptides; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*; D011506:Proteins / Q000502:physiology*; D006435:Renal Dialysis; D013450:Sulfones / Q000494:pharmacology*; D013499:Surface Properties / Q000187:drug effects
chemical_list: D020099:Coated Materials, Biocompatible; D008567:Membranes, Artificial; D010455:Peptides; D011108:Polymers; D011506:Proteins; D013450:Sulfones; C086589:pilH protein, Pseudomonas aeruginosa; D036781:Fimbriae Proteins; C017662:polysulfone P 1700; D011092:Polyethylene Glycols