title: Synthesis and applications of polyamine amino acid residues: improving the bioactivity of an analgesic neuropeptide, neurotensin.
abstract: Conjugated polyamines are potential carriers for biotherapeutics targeting the central nervous system. We describe an efficient synthesis of a polyamine-based amino acid, lysine-trimethylene(diNosyl)-spermine(triBoc) with Dde or Fmoc orthogonal protecting groups. This nonnatural amino acid was incorporated into a neurotensin analogue using standard Fmoc-based protocols. The analogue maintained high affinity and agonist potency for neurotensin receptors and exhibited dramatically improved analgesia in mice. Our work provides a basis for use of polyamine amino acids in polypeptides.
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Utah, Salt Lake City, Utah 84108, USA.
authors.forename: Liuyin
authors.initials: L
authors.lastname: Zhang
authors.forename: Hee-Kyoung
authors.initials: HK
authors.lastname: Lee
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Pruess
authors.forename: H Steve
authors.initials: HS
authors.lastname: White
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Bulaj
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D009496:Neurotensin / Q000737:chemistry / Q000494:pharmacology*; D011073:Polyamines / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D011073:Polyamines; D009496:Neurotensin