title: An optimized chemical synthesis of human relaxin-2.
abstract: Human gene 2 relaxin (RLX) is a member of the insulin superfamily and is a multi-functional factor playing a vital role in pregnancy, aging, fibrosis, cardioprotection, vasodilation, inflammation, and angiogenesis. RLX is currently applied in clinical trials to cure among others acute heart failure, fibrosis, and preeclampsia. The synthesis of RLX by chemical methods is difficult because of the insolubility of its B-chain and the required laborious and low yielding site-directed combination of its A (RLXA) and B (RLXB) chains. We report here that oxidation of the Met(25) residue of RLXB improves its solubility, allowing its effective solid-phase synthesis and application in random interchain combination reactions with RLXA. Linear Met(O)(25)-RLX B-chain (RLXBO) reacts with a mixture of isomers of bicyclic A-chain (bcRLXA) giving exclusively the native interchain combination. Applying this method Met(O)(25)-RLX (RLXO) was obtained in 62% yield and was easily converted to RLX in 78% yield, by reduction with ammonium iodide.
authors.affiliation: Department of Chemistry, University of Patras, Rion-Patras, Greece. barlos@cblpatras.gr
authors.forename: Kostas K
authors.initials: KK
authors.lastname: Barlos
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Gatos
authors.forename: Zoe
authors.initials: Z
authors.lastname: Vasileiou
authors.forename: Kleomenis
authors.initials: K
authors.lastname: Barlos
mesh_terms: D000595:Amino Acid Sequence; D002853:Chromatography, Liquid; D006801:Humans; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D012065:Relaxin / Q000138:chemical synthesis*; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet
chemical_list: C095068:RLN2 protein, human; D012065:Relaxin