title: Deferasirox-TAT(47-57) peptide conjugate as a water soluble, bifunctional iron chelator with potential use in neuromedicine.
abstract: Deferasirox (DFX), an orally active and clinically approved iron chelator, is being used extensively for the treatment of iron overload. However, its water insolubility makes it cumbersome for practical use. In addition to this, the low efficacy of DFX to remove brain iron prompted us to synthesize and evaluate a DFX-TAT(47-57) peptide conjugate for its iron chelation properties and permeability across RBE4 cell line, an in vitro model of the blood-brain barrier. The water-soluble conjugate was able to remove labile iron from buffered solution as well as from iron overloaded sera, and the permeability of DFX-TAT(47-57) conjugate into RBE4 cells was not affected compared to parent deferasirox. The iron bound conjugate was also able to translocate through the cell membrane.
authors.affiliation: Departamento de Química Fundamental, Universidade de São Paulo, Av. Lineu Prestes 748, São Paulo, 05508-000, Brazil.|Bio-Organic Division, Bhabha Atomic Research Centre, Trombay, Mumbai, India.
authors.forename: Dibakar
authors.initials: D
authors.lastname: Goswami
authors.affiliation: Departamento de Química Fundamental, Universidade de São Paulo, Av. Lineu Prestes 748, São Paulo, 05508-000, Brazil.
authors.forename: Hector A
authors.initials: HA
authors.lastname: Vitorino
authors.affiliation: Departamento de Química Fundamental, Universidade de São Paulo, Av. Lineu Prestes 748, São Paulo, 05508-000, Brazil.
authors.forename: Roxana Y P
authors.initials: RY
authors.lastname: Alta
authors.affiliation: Departamento de Química Fundamental, Universidade de São Paulo, Av. Lineu Prestes 748, São Paulo, 05508-000, Brazil.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Silvestre
authors.affiliation: Departamento de Química Fundamental, Universidade de São Paulo, Av. Lineu Prestes 748, São Paulo, 05508-000, Brazil.
authors.forename: Cassiana S
authors.initials: CS
authors.lastname: Nomura
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Lineu Prestes 748, São Paulo, 05508-000, Brazil.
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Machini
authors.affiliation: Departamento de Química Fundamental, Universidade de São Paulo, Av. Lineu Prestes 748, São Paulo, 05508-000, Brazil. breno@iq.usp.br.
authors.forename: Breno P
authors.initials: BP
authors.lastname: Espósito
mesh_terms: D000818:Animals; D001565:Benzoates / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*; D001812:Blood-Brain Barrier / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects; D000077588:Deferasirox; D006801:Humans; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*; D019190:Iron Overload / Q000188:drug therapy* / Q000473:pathology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*; D051381:Rats; D012995:Solubility; D014230:Triazoles / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*; D014867:Water / Q000737:chemistry; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D010446:Peptide Fragments; D014230:Triazoles; D054322:tat Gene Products, Human Immunodeficiency Virus; C497137:tat peptide (47-57), Human immunodeficiency virus 1; D014867:Water; D000077588:Deferasirox
keywords: Blood–brain barrier; Chelation; Deferasirox; Iron; Overload; Peptide; Tat