Synthesis and applications of polyamine amino acid residues: improving the bioactivity of an analgesic neuropeptide, neurotensin.
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.
Zhang
Liuyin
L
Department of Medicinal Chemistry, College of Pharmacy, University of Utah, Salt Lake City, Utah 84108, USA.
Lee
Hee-Kyoung
HK
Pruess
Timothy H
TH
White
H Steve
HS
Bulaj
Grzegorz
G
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D009496:Neurotensin / Q000737:chemistry / Q000494:pharmacology*; D011073:Polyamines / Q000737:chemistry*
D000596:Amino Acids; D011073:Polyamines; D009496:Neurotensin