title: Conotoxin engineering: dual pharmacophoric noradrenaline transport inhibitor/integrin binding peptide with improved stability.
abstract: A dual-pharmacophoric peptide was engineered by grafting the integrin binding RGD motif between the C- and N-termini of a disulfide-rich noradrenaline transporter inhibiting χ-conotoxin resulting in a stable backbone cyclized peptide. The construct maintained two independent biological activities and showed increased plasma stability with no adverse effects observed following administration to rats, highlighting the potential value of pharmacophore grafting into constrained peptide scaffolds.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St Lucia 4072, Queensland, Australia.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Dekan
authors.forename: Ching-I Anderson
authors.initials: CI
authors.lastname: Wang
authors.forename: Robert K
authors.initials: RK
authors.lastname: Andrews
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lewis
authors.forename: Paul F
authors.initials: PF
authors.lastname: Alewood
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects*; D020916:Conotoxins / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008958:Models, Molecular; D009638:Norepinephrine / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors; D009842:Oligopeptides; D010456:Peptides, Cyclic / Q000378:metabolism; D015202:Protein Engineering / Q000379:methods*; D055550:Protein Stability; D051381:Rats
chemical_list: D020916:Conotoxins; D016023:Integrins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D009842:Oligopeptides; D010456:Peptides, Cyclic; C047981:arginyl-glycyl-aspartic acid; D009638:Norepinephrine