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Fmoc chemistry compatible thio-ligation assembly of proteins
Authors:Sara Biancalana  Derek Hudson  Michael F Songster and Stewart A Thompson
Institution:(1) Biosearch Technologies, Inc., 81 Digital Drive, Novato, CA 94949, USA;(2) Berlex Biosciences, 15049 San Pablo Avenue, P.O. Box 4099, Richmond, CA 94804, USA;(3) Berlex Biosciences, 15049 San Pablo Avenue, P.O. Box 4099, Richmond, CA 94804, USA;(4) Present address: Inhale Therapeutic Systems, 150 Industrial Rd., San Carlos, CA, 94070
Abstract:We describe, and compare, two methods which enable theassembly of proteins from peptide thioester fragmentsprepared by Fmoc chemistry mediated solid phase synthesis. The first, which utilizes iso-thiouronium salts,allows formation of thiophenyl esters directly frompartially protected peptides, either in solution or onresin. The second uses lsquosulfonamidersquo based safety-catchresins. Data on yields, generality and potential for side-reactions are provided.
Keywords:chemoselective ligation  Fmoc-methodology  iso-thiouronium salts  Kenner safety catch resin  native chemical ligation  peptide thioesters  peptide isomerisation  safety-catch linkers  solid-phase synthesis  thioester exchange
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