title: Site specific 1:1 opioid:albumin conjugate with in vitro activity and long in vivo duration.
abstract: A site-specific 1:1 dynorphin A-(1-13)-NH(2) derivative conjugated specifically to Cys 34 on human serum albumin (CCI-1035) was shown to be an opioid receptor agonist in vitro and to be a long lasting antinociceptive agent when administered intravenously to mice as assessed by an acetic acid writhing assay. When 10 micromol/kg of CCI-1035 was administered to mice, rapid antinociception was observed within 5 min following intravenous bolus injection and was sustained beyond 8 h. Antinociceptive activity was absent in a heat induced pain model using a mouse tail-flick assay. This finding represents the first report of a 1:1 albumin opioid conjugate retaining potent in vivo activity equal to or greater than dynorphin A, accompanied by a dramatic extension in duration of action. This novel site-specific bioconjugation technology produces an agent that may be useful for peripheral pain therapy.
authors.affiliation: ConjuChem, Inc., 225 President-Kennedy Avenue, Third Floor, Suite 3950, Montréal (Quebéc), Canada H2X 3Y8.
authors.forename: D L
authors.initials: DL
authors.lastname: Holmes
authors.forename: K
authors.initials: K
authors.lastname: Thibaudeau
authors.forename: B
authors.initials: B
authors.lastname: L'Archevêque
authors.forename: P G
authors.initials: PG
authors.lastname: Milner
authors.forename: A M
authors.initials: AM
authors.lastname: Ezrin
authors.forename: D P
authors.initials: DP
authors.lastname: Bridon
mesh_terms: D000595:Amino Acid Sequence; D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D004399:Dynorphins / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry*
chemical_list: D000700:Analgesics; D010446:Peptide Fragments; D012709:Serum Albumin; C026843:dynorphin (1-13); D004399:Dynorphins