title: Phosphate ester serum albumin affinity tags greatly improve peptide half-life in vivo.
abstract: A series of phosphate ester based small molecules designed to 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 exhibited high affinity for both rabbit and human serum albumin when passed through liquid chromatographic columns with serum albumins incorporated into the stationary phase. The peptides were then administered intravenously to rabbits and found to have a greater than 50-fold increase in plasma half life. The highest affinity peptides showed a reduction in bioactivity consistent with their sequestration away from their protein target in the presence of 0.1% rabbit serum albumin.
authors.affiliation: Department of Protein Engineering, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Kerry
authors.initials: K
authors.lastname: Zobel
authors.forename: Michael F T
authors.initials: MF
authors.lastname: Koehler
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
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000737:chemistry* / Q000493:pharmacokinetics; D001798:Blood Proteins / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D010755:Organophosphates / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry* / Q000493:pharmacokinetics; D010710:Phosphates; D011485:Protein Binding; D011817:Rabbits; D012709:Serum Albumin / Q000737:chemistry*; D013997:Time Factors
chemical_list: D000925:Anticoagulants; D001798:Blood Proteins; D010755:Organophosphates; D010455:Peptides; D010710:Phosphates; D012709:Serum Albumin