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An optimized chemical synthesis of human relaxin‐2
Author(s) -
Barlos Kostas K.,
Gatos Dimitrios,
Vasileiou Zoe,
Barlos Kleomenis
Publication year - 2010
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.1221
Subject(s) - relaxin , chemistry , vasodilation , yield (engineering) , combinatorial chemistry , pharmacology , stereochemistry , biochemistry , medicine , hormone , endocrinology , materials science , metallurgy
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. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.