title: Synthesis and biological activity of mouse hepcidin peptide analogs containing three disulfide bridges: manual and microwave-assisted solid-phase peptide synthesis.
abstract: Hepcidin, a 25 amino acid peptide hormone containing a complex network of four disulfide bonds is the hormone regulator of iron homeostasis. Three bridges synthetic peptide analogs have been prepared following two synthetic strategies and two oxidation procedures: i) a microwave-assisted solid phase synthesis followed by air oxidation of the six free cysteines ii) a manual solid phase synthesis followed by stepwise deprotection and oxidation of cysteine pairs. All the peptides with different connectivities have been characterized by MALDI ToF spectrometry, and tested for their ability to degrade the cellular iron exporter, ferroportin. While linear peptides are inactive, the one-bridge and two-bridge peptides retaining protected cysteines by bulky substituents are active. Similarly, the three-bridge peptides are active irrespective of their disulfide connectivities.
authors.affiliation: Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, UMR 8601 Universite Paris Descartes, CNRS, 45 Rue des Saints Peres, 75270 Paris Cedex 06, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Khemtemourian
authors.forename: Nicolas
authors.initials: N
authors.lastname: Desbenoit
authors.forename: Pavar
authors.initials: P
authors.lastname: Mahesh
authors.forename: Sunanda
authors.initials: S
authors.lastname: Chatterjee
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Deschemin
authors.forename: Sophie
authors.initials: S
authors.lastname: Vaulont
authors.forename: Alain
authors.initials: A
authors.lastname: Tomas
authors.forename: Marie-Agnes
authors.initials: MA
authors.lastname: Sari
authors.forename: Isabelle
authors.initials: I
authors.lastname: Artaud
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D004220:Disulfides / Q000138:chemical synthesis* / Q000737:chemistry; D004353:Drug Evaluation, Preclinical; D015870:Gene Expression / Q000187:drug effects; D064451:Hepcidins; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008872:Microwaves; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017510:Protein Folding; D060327:Solid-Phase Synthesis Techniques / Q000295:instrumentation / Q000379:methods*; D000098742:Ferroportin
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; D004220:Disulfides; C579599:Hamp protein, mouse; D064451:Hepcidins; D010455:Peptides; D000098742:Ferroportin; D003545:Cysteine