title: Albumin affinity tags increase peptide half-life in vivo.
abstract: Small organic molecules that bind tightly to serum albumin were applied to the amino terminus of an anticoagulant peptide in an effort to increase its protein binding in vivo. The tagged peptides were evaluated for their ability to be retained on liquid chromatographic columns with serum albumins incorporated into the stationary phase. Those which demonstrated significant affinity were administered intravenously to rabbits and found to have significantly increased plasma half-lives. Novel affinity tags were identified by appending a focused library of compounds to a model tetrapeptide and evaluating the resulting compounds' ability to bind to the serum albumin columns. The most promising were synthesized as the full length peptides and again evaluated in vivo. They were found to have still longer half-lives than the first generation compounds.
authors.affiliation: Department of Protein Engineering, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. mkoehler@gene.com
authors.forename: Michael F T
authors.initials: MF
authors.lastname: Koehler
authors.forename: Kerry
authors.initials: K
authors.lastname: Zobel
authors.forename: Maureen H
authors.initials: MH
authors.lastname: Beresini
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Caris
authors.forename: Daniel
authors.initials: D
authors.lastname: Combs
authors.forename: Brian D
authors.initials: BD
authors.lastname: Paasch
authors.forename: Robert A
authors.initials: RA
authors.lastname: Lazarus
mesh_terms: D000345:Affinity Labels / Q000737:chemistry*; D000418:Albumins / Q000737:chemistry*; D000818:Animals; D000925:Anticoagulants / Q000737:chemistry* / Q000493:pharmacokinetics; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D015942:Factor VIIa / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D010455:Peptides / Q000737:chemistry* / Q000493:pharmacokinetics; D011485:Protein Binding; D011817:Rabbits; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000345:Affinity Labels; D000418:Albumins; D000925:Anticoagulants; D010455:Peptides; D015942:Factor VIIa